Bryostatin-1 enhances the proliferation and functionality of exhausted CD8+ T cells by upregulating MAP Kinase 11

Bryostatin-1, a potent agonist of the protein kinase C, has been studied for HIV and cancer therapies. In HIV research, it has shown anti-HIV effects during acute infection and reactivation of latent HIV in chronic infection. As effective CD8+ T cell responses are essential for eliminating reactivat...

Celý popis

Uložené v:

Podrobná bibliografia
Vydané v:	Frontiers in immunology Ročník 15; s. 1509874
Hlavní autori:	Li, Ling, Zhao, Manzhi, van Meurs, Marjan, Brouwers-Haspels, Inge, den Dekker, Renske J. H., Wilmsen, Merel E. P., Grashof, Dwin G. B., van de Werken, Harmen J. G., Rao, Shringar, Rokx, Casper, Mueller, Yvonne M., Katsikis, Peter D.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	Switzerland Frontiers Media SA 14.01.2025 Frontiers Media S.A
Predmet:	Animals bryostatin-1 Bryostatins - pharmacology Cancer Cancer immunotherapy Cancer therapies CD8 antigen CD8-Positive T-Lymphocytes - drug effects CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - metabolism Cell growth Cell proliferation Cell Proliferation - drug effects Chronic infection Clinical trials Cytotoxicity Down-regulation exhausted CD8+ T cells Flow cytometry Hepatocyte nuclear factor 1 HIV HIV Infections - drug therapy HIV Infections - immunology HIV-1 - immunology Human immunodeficiency virus Humans IFN-γ production Immunity (Disease) Immunology Infections Kinases Lymphocyte Activation - drug effects Lymphocytes Lymphocytes T MAP kinase MAP kinase 11 Mice PD-1 protein Peptides Protein kinase C Proteins Ribonucleic acid RNA Sequence analysis Transcription factors Up-Regulation γ-Interferon HIV bryostatin-1 IFN-γ production exhausted CD8+ T cells MAP kinase 11
ISSN:	1664-3224, 1664-3224
On-line prístup:	Získať plný text
Tagy:	Pridať tag Žiadne tagy, Buďte prvý, kto otaguje tento záznam!

Abstract	Bryostatin-1, a potent agonist of the protein kinase C, has been studied for HIV and cancer therapies. In HIV research, it has shown anti-HIV effects during acute infection and reactivation of latent HIV in chronic infection. As effective CD8+ T cell responses are essential for eliminating reactivated virus and achieving a cure, it is important to investigate how bryostatin-1 affects HIV-specific CD8+ T cells. HIV-specific CD8+ T cells often become exhausted, showing reduced proliferative potential and impaired cytokine production, a dysfunction also observed in cancer. Therefore, we further investigated how bryostatin-1 directly impacts exhausted CD8+ T cells. PBMCs from people with HIV (PWH) were treated with bryostatin-1 and tracked with proliferation dye for cell expansion. One day 6, HIV-specific CD8+ T cells were detected by tetramers staining and examined by flow cytometry. By utilizing an established murine T cell exhaustion system, changes in inhibitory receptors, transcription factors, cytokine production and killing capacity of bryostatin-1 treated exhausted CD8+ T cells were determined by flow cytometry. RNA-seq analysis was performed to study transcriptional changes in these cells. We found that bryostatin-1 improved the expansion and decreased PD-1 expression of HIV-specific CD8+ T cells. Bryostatin-1 enhanced the functionality and proliferation while decreasing inhibitory receptor expression of generated exhausted CD8+ T cells. Bryostatin-1 upregulated TCF-1 and decreased TOX expression. These changes were confirmed through RNA-seq analysis. RNA-seq revealed that mitogen-activated protein kinases (MAPK) 11 was significantly downregulated in exhausted CD8+ T cells, however, it greatly upregulated after bryostatin-1 treatment. Inhibition of MAPK11 in bryostatin-1-treated cells blocked the increased proliferation and IFN-γ production induced by bryostatin-1, but did not affect other bryostatin-1 induced effects, such as the reduction of inhibitory receptors. Our data demonstrate that bryostatin-1 induces a MAPK 11-dependent improvement in the proliferative and functional capacity of exhausted T cells. This study provides a rationale for bryostatin-1's potential to help eradicate the HIV reservoir during treatment, and it may also contribute to cancer immunotherapy by functionally improving exhausted CD8+ T cells.
AbstractList	Bryostatin-1, a potent agonist of the protein kinase C, has been studied for HIV and cancer therapies. In HIV research, it has shown anti-HIV effects during acute infection and reactivation of latent HIV in chronic infection. As effective CD8+ T cell responses are essential for eliminating reactivated virus and achieving a cure, it is important to investigate how bryostatin-1 affects HIV-specific CD8+ T cells. HIV-specific CD8+ T cells often become exhausted, showing reduced proliferative potential and impaired cytokine production, a dysfunction also observed in cancer. Therefore, we further investigated how bryostatin-1 directly impacts exhausted CD8+ T cells.IntroductionBryostatin-1, a potent agonist of the protein kinase C, has been studied for HIV and cancer therapies. In HIV research, it has shown anti-HIV effects during acute infection and reactivation of latent HIV in chronic infection. As effective CD8+ T cell responses are essential for eliminating reactivated virus and achieving a cure, it is important to investigate how bryostatin-1 affects HIV-specific CD8+ T cells. HIV-specific CD8+ T cells often become exhausted, showing reduced proliferative potential and impaired cytokine production, a dysfunction also observed in cancer. Therefore, we further investigated how bryostatin-1 directly impacts exhausted CD8+ T cells.PBMCs from people with HIV (PWH) were treated with bryostatin-1 and tracked with proliferation dye for cell expansion. One day 6, HIV-specific CD8+ T cells were detected by tetramers staining and examined by flow cytometry. By utilizing an established in vitro murine T cell exhaustion system, changes in inhibitory receptors, transcription factors, cytokine production and killing capacity of bryostatin-1 treated exhausted CD8+ T cells were determined by flow cytometry. RNA-seq analysis was performed to study transcriptional changes in these cells.MethodsPBMCs from people with HIV (PWH) were treated with bryostatin-1 and tracked with proliferation dye for cell expansion. One day 6, HIV-specific CD8+ T cells were detected by tetramers staining and examined by flow cytometry. By utilizing an established in vitro murine T cell exhaustion system, changes in inhibitory receptors, transcription factors, cytokine production and killing capacity of bryostatin-1 treated exhausted CD8+ T cells were determined by flow cytometry. RNA-seq analysis was performed to study transcriptional changes in these cells.We found that bryostatin-1 improved the expansion and decreased PD-1 expression of HIV-specific CD8+ T cells. Bryostatin-1 enhanced the functionality and proliferation while decreasing inhibitory receptor expression of in vitro generated exhausted CD8+ T cells. Bryostatin-1 upregulated TCF-1 and decreased TOX expression. These changes were confirmed through RNA-seq analysis. RNA-seq revealed that mitogen-activated protein kinases (MAPK) 11 was significantly downregulated in exhausted CD8+ T cells, however, it greatly upregulated after bryostatin-1 treatment. Inhibition of MAPK11 in bryostatin-1-treated cells blocked the increased proliferation and IFN-γ production induced by bryostatin-1, but did not affect other bryostatin-1 induced effects, such as the reduction of inhibitory receptors.ResultsWe found that bryostatin-1 improved the expansion and decreased PD-1 expression of HIV-specific CD8+ T cells. Bryostatin-1 enhanced the functionality and proliferation while decreasing inhibitory receptor expression of in vitro generated exhausted CD8+ T cells. Bryostatin-1 upregulated TCF-1 and decreased TOX expression. These changes were confirmed through RNA-seq analysis. RNA-seq revealed that mitogen-activated protein kinases (MAPK) 11 was significantly downregulated in exhausted CD8+ T cells, however, it greatly upregulated after bryostatin-1 treatment. Inhibition of MAPK11 in bryostatin-1-treated cells blocked the increased proliferation and IFN-γ production induced by bryostatin-1, but did not affect other bryostatin-1 induced effects, such as the reduction of inhibitory receptors.Our data demonstrate that bryostatin-1 induces a MAPK 11-dependent improvement in the proliferative and functional capacity of exhausted T cells. This study provides a rationale for bryostatin-1's potential to help eradicate the HIV reservoir during treatment, and it may also contribute to cancer immunotherapy by functionally improving exhausted CD8+ T cells.DiscussionOur data demonstrate that bryostatin-1 induces a MAPK 11-dependent improvement in the proliferative and functional capacity of exhausted T cells. This study provides a rationale for bryostatin-1's potential to help eradicate the HIV reservoir during treatment, and it may also contribute to cancer immunotherapy by functionally improving exhausted CD8+ T cells. IntroductionBryostatin-1, a potent agonist of the protein kinase C, has been studied for HIV and cancer therapies. In HIV research, it has shown anti-HIV effects during acute infection and reactivation of latent HIV in chronic infection. As effective CD8+ T cell responses are essential for eliminating reactivated virus and achieving a cure, it is important to investigate how bryostatin-1 affects HIV-specific CD8+ T cells. HIV-specific CD8+ T cells often become exhausted, showing reduced proliferative potential and impaired cytokine production, a dysfunction also observed in cancer. Therefore, we further investigated how bryostatin-1 directly impacts exhausted CD8+ T cells.MethodsPBMCs from people with HIV (PWH) were treated with bryostatin-1 and tracked with proliferation dye for cell expansion. One day 6, HIV-specific CD8+ T cells were detected by tetramers staining and examined by flow cytometry. By utilizing an established in vitro murine T cell exhaustion system, changes in inhibitory receptors, transcription factors, cytokine production and killing capacity of bryostatin-1 treated exhausted CD8+ T cells were determined by flow cytometry. RNA-seq analysis was performed to study transcriptional changes in these cells.ResultsWe found that bryostatin-1 improved the expansion and decreased PD-1 expression of HIV-specific CD8+ T cells. Bryostatin-1 enhanced the functionality and proliferation while decreasing inhibitory receptor expression of in vitro generated exhausted CD8+ T cells. Bryostatin-1 upregulated TCF-1 and decreased TOX expression. These changes were confirmed through RNA-seq analysis. RNA-seq revealed that mitogen-activated protein kinases (MAPK) 11 was significantly downregulated in exhausted CD8+ T cells, however, it greatly upregulated after bryostatin-1 treatment. Inhibition of MAPK11 in bryostatin-1-treated cells blocked the increased proliferation and IFN-γ production induced by bryostatin-1, but did not affect other bryostatin-1 induced effects, such as the reduction of inhibitory receptors.DiscussionOur data demonstrate that bryostatin-1 induces a MAPK 11-dependent improvement in the proliferative and functional capacity of exhausted T cells. This study provides a rationale for bryostatin-1's potential to help eradicate the HIV reservoir during treatment, and it may also contribute to cancer immunotherapy by functionally improving exhausted CD8+ T cells. Bryostatin-1, a potent agonist of the protein kinase C, has been studied for HIV and cancer therapies. In HIV research, it has shown anti-HIV effects during acute infection and reactivation of latent HIV in chronic infection. As effective CD8+ T cell responses are essential for eliminating reactivated virus and achieving a cure, it is important to investigate how bryostatin-1 affects HIV-specific CD8+ T cells. HIV-specific CD8+ T cells often become exhausted, showing reduced proliferative potential and impaired cytokine production, a dysfunction also observed in cancer. Therefore, we further investigated how bryostatin-1 directly impacts exhausted CD8+ T cells. PBMCs from people with HIV (PWH) were treated with bryostatin-1 and tracked with proliferation dye for cell expansion. One day 6, HIV-specific CD8+ T cells were detected by tetramers staining and examined by flow cytometry. By utilizing an established murine T cell exhaustion system, changes in inhibitory receptors, transcription factors, cytokine production and killing capacity of bryostatin-1 treated exhausted CD8+ T cells were determined by flow cytometry. RNA-seq analysis was performed to study transcriptional changes in these cells. We found that bryostatin-1 improved the expansion and decreased PD-1 expression of HIV-specific CD8+ T cells. Bryostatin-1 enhanced the functionality and proliferation while decreasing inhibitory receptor expression of generated exhausted CD8+ T cells. Bryostatin-1 upregulated TCF-1 and decreased TOX expression. These changes were confirmed through RNA-seq analysis. RNA-seq revealed that mitogen-activated protein kinases (MAPK) 11 was significantly downregulated in exhausted CD8+ T cells, however, it greatly upregulated after bryostatin-1 treatment. Inhibition of MAPK11 in bryostatin-1-treated cells blocked the increased proliferation and IFN-γ production induced by bryostatin-1, but did not affect other bryostatin-1 induced effects, such as the reduction of inhibitory receptors. Our data demonstrate that bryostatin-1 induces a MAPK 11-dependent improvement in the proliferative and functional capacity of exhausted T cells. This study provides a rationale for bryostatin-1's potential to help eradicate the HIV reservoir during treatment, and it may also contribute to cancer immunotherapy by functionally improving exhausted CD8+ T cells.
Author	Rao, Shringar Brouwers-Haspels, Inge Grashof, Dwin G. B. Li, Ling Rokx, Casper Zhao, Manzhi Mueller, Yvonne M. Wilmsen, Merel E. P. van Meurs, Marjan van de Werken, Harmen J. G. Katsikis, Peter D. den Dekker, Renske J. H.
AuthorAffiliation	2 Department of Biochemistry, Erasmus University Medical Center , Rotterdam , Netherlands 1 Department of Immunology, Erasmus University Medical Center , Rotterdam , Netherlands 3 Department of Internal Medicine, and Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center , Rotterdam , Netherlands
AuthorAffiliation_xml	– name: 2 Department of Biochemistry, Erasmus University Medical Center , Rotterdam , Netherlands – name: 3 Department of Internal Medicine, and Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center , Rotterdam , Netherlands – name: 1 Department of Immunology, Erasmus University Medical Center , Rotterdam , Netherlands
Author_xml	– sequence: 1 givenname: Ling surname: Li fullname: Li, Ling – sequence: 2 givenname: Manzhi surname: Zhao fullname: Zhao, Manzhi – sequence: 3 givenname: Marjan surname: van Meurs fullname: van Meurs, Marjan – sequence: 4 givenname: Inge surname: Brouwers-Haspels fullname: Brouwers-Haspels, Inge – sequence: 5 givenname: Renske J. H. surname: den Dekker fullname: den Dekker, Renske J. H. – sequence: 6 givenname: Merel E. P. surname: Wilmsen fullname: Wilmsen, Merel E. P. – sequence: 7 givenname: Dwin G. B. surname: Grashof fullname: Grashof, Dwin G. B. – sequence: 8 givenname: Harmen J. G. surname: van de Werken fullname: van de Werken, Harmen J. G. – sequence: 9 givenname: Shringar surname: Rao fullname: Rao, Shringar – sequence: 10 givenname: Casper surname: Rokx fullname: Rokx, Casper – sequence: 11 givenname: Yvonne M. surname: Mueller fullname: Mueller, Yvonne M. – sequence: 12 givenname: Peter D. surname: Katsikis fullname: Katsikis, Peter D.
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/39877358$$D View this record in MEDLINE/PubMed
BookMark	eNp9kstu1DAUhi1UREvpC7BAltggoQy-JbZXqAy3iiJYlLXlOPaMR4k9tRPEvD3OzBS1XeCNL-c_n3-dc56DkxCDBeAlRgtKhXzn_DBMC4IIW-AaScHZE3CGm4ZVlBB2cu98Ci5y3qCymKSU1s_AKS16TmtxBm4_pF3Mox59qDC0Ya2DsRmOawu3Kfbe2VRiMUAdOuimYOaL7v24g9FB-2etpzzaDi4_irfwBhrb9xm2Ozhtk11N_cxdwe-XP-E3H3S2EOMX4KnTfbYXx_0c_Pr86Wb5tbr-8eVqeXldGSb5WLUdIUYgihGjjWiclLppdUe44ZZgzUQjOs6RITVuJS5R3Jq27rARAhNGBT0HVwduF_VGbZMfdNqpqL3aP8S0UjqN3vRWYWGQqSVtC5MxW8u2kc51raMN1UjQwnp_YG2ndrCdsWFMun8AfRgJfq1W8bfCmHOC5ezmzZGQ4u1k86gGn-dq6WDjlBXFDZIMkWb-7PUj6SZOqRS9qAgXhDOE6qJ6dd_SPy93rS0CcRCYFHNO1injx30vi0PfK4zUPEhqP0hqHiR1HKSSSh6l3tH_k_QXA-XLkQ
CitedBy_id	crossref_primary_10_3390_md23070283
Cites_doi	10.1002/1097-0142(20000801)89:3<615::AID-CNCR17>3.0.CO;2-J 10.1182/blood.V89.9.3402 10.1093/jnci/85.22.1812 10.12688/f1000research 10.3389/fimmu.2019.00169 10.4049/jimmunol.162.7.3819 10.1074/jbc.272.23.15023 10.1016/j.immuni.2018.12.021 10.1128/JVI.01153-09 10.1038/ni.2035 10.1038/nri3862 10.1517/13543784.8.12.2189 10.1182/blood.V75.6.1319.1319 10.1038/s41586-019-1326-9 10.1038/s41467-020-15742-7 10.1126/science.278.5341.1295 10.1128/JVI.02383-07 10.1097/QAD.0000000000001064 10.1016/S0192-0561(00)00027-8 10.1016/j.ebiom.2016.04.019 10.4049/jimmunol.180.10.6490 10.1006/cimm.1994.1267 10.3109/13880209.2013.804100 10.1097/QAD.0b013e32832e6634 10.1084/jem.20150598 10.1038/srep12442 10.1038/nm1482 10.1172/JCI80142 10.1038/bjc.1995.356 10.3791/2381 10.1128/MCB.20.3.936-946.2000 10.1016/j.immuni.2018.04.030 10.1097/00008390-199912000-00010 10.1016/0192-0561(90)90110-9 10.2174/157016210793499312 10.1182/blood.V96.9.3094 10.1038/s41586-019-1325-x 10.4049/jimmunol.0800997 10.1081/CNV-120025095 10.1006/bbrc.1995.2413 10.1073/pnas.1704227114 10.1186/s13059-014-0550-8 10.1016/j.immuni.2018.04.026 10.1074/jbc.M401656200 10.1152/ajpcell.1996.271.1.C304 10.1038/387183a0 10.1023/A:1010628903248 10.1074/jbc.M110.135921 10.1093/intimm/dxh130 10.1038/nm.2232 10.1172/JCI80566 10.1016/S0161-5890(00)00078-X 10.2174/1568026620666200325110444 10.1002/med.21727 10.1097/QAD.0000000000000788 10.1097/QAD.0000000000002406 10.1038/sj.bjc.6601321 10.1097/00002371-199208000-00001 10.4049/jimmunol.167.9.4828 10.1016/j.bbrc.2004.02.101 10.1126/sciimmunol.abb9726 10.1016/j.phrs.2018.10.023 10.1038/s41587-020-0439-x 10.1111/imr.v292.1 10.1371/journal.ppat.1003174 10.1186/s12977-015-0144-x 10.1074/jbc.272.32.20245 10.1097/00007890-199106000-00017 10.1016/0022-4804(92)90126-K 10.1128/jvi.01953-21 10.1038/nature05115 10.3109/10428199309148517 10.1006/jsre.2001.6181 10.1371/journal.ppat.1008555 10.1111/j.1527-3458.2006.00001.x 10.4049/jimmunol.141.10.3263 10.1038/s41590-019-0312-6 10.1016/j.ebiom.2022.103840 10.1038/bjc.1998.680 10.1371/journal.pone.0011160 10.1073/pnas.200363097 10.1038/nbt.3820 10.1016/j.immuni.2016.07.011 10.1086/jid.2005.191.issue-9 10.1007/s00262-009-0666-y
ContentType	Journal Article
Copyright	Copyright © 2025 Li, Zhao, van Meurs, Brouwers-Haspels, den Dekker, Wilmsen, Grashof, van de Werken, Rao, Rokx, Mueller and Katsikis. 2025. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. Copyright © 2025 Li, Zhao, van Meurs, Brouwers-Haspels, den Dekker, Wilmsen, Grashof, van de Werken, Rao, Rokx, Mueller and Katsikis 2025 Li, Zhao, van Meurs, Brouwers-Haspels, den Dekker, Wilmsen, Grashof, van de Werken, Rao, Rokx, Mueller and Katsikis
Copyright_xml	– notice: Copyright © 2025 Li, Zhao, van Meurs, Brouwers-Haspels, den Dekker, Wilmsen, Grashof, van de Werken, Rao, Rokx, Mueller and Katsikis. – notice: 2025. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. – notice: Copyright © 2025 Li, Zhao, van Meurs, Brouwers-Haspels, den Dekker, Wilmsen, Grashof, van de Werken, Rao, Rokx, Mueller and Katsikis 2025 Li, Zhao, van Meurs, Brouwers-Haspels, den Dekker, Wilmsen, Grashof, van de Werken, Rao, Rokx, Mueller and Katsikis
DBID	AAYXX CITATION CGR CUY CVF ECM EIF NPM 3V. 7X7 7XB 88E 8C1 8FE 8FH 8FI 8FJ 8FK ABUWG AFKRA AZQEC BBNVY BENPR BHPHI CCPQU DWQXO FYUFA GHDGH GNUQQ HCIFZ K9. LK8 M0S M1P M7P PHGZM PHGZT PIMPY PJZUB PKEHL PPXIY PQEST PQGLB PQQKQ PQUKI 7X8 5PM DOA
DOI	10.3389/fimmu.2024.1509874
DatabaseName	CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed ProQuest Central (Corporate) Health & Medical Collection ProQuest Central (purchase pre-March 2016) Medical Database (Alumni Edition) Public Health Database ProQuest SciTech Collection ProQuest Natural Science Collection ProQuest Hospital Collection Hospital Premium Collection (Alumni Edition) ProQuest Central (Alumni) (purchase pre-March 2016) ProQuest Central (Alumni) ProQuest Central UK/Ireland ProQuest Central Essentials Biological Science Collection ProQuest Central Natural Science Collection ProQuest One ProQuest Central Health Research Premium Collection Health Research Premium Collection (Alumni) ProQuest Central Student SciTech Premium Collection ProQuest Health & Medical Complete (Alumni) Biological Sciences ProQuest Health & Medical Collection Medical Database Biological Science Database ProQuest Central Premium ProQuest One Academic (New) Publicly Available Content Database ProQuest Health & Medical Research Collection ProQuest One Academic Middle East (New) ProQuest One Health & Nursing ProQuest One Academic Eastern Edition (DO NOT USE) ProQuest One Applied & Life Sciences ProQuest One Academic (retired) ProQuest One Academic UKI Edition MEDLINE - Academic PubMed Central (Full Participant titles) DOAJ Directory of Open Access Journals
DatabaseTitle	CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) Publicly Available Content Database ProQuest Central Student ProQuest One Academic Middle East (New) ProQuest Central Essentials ProQuest Health & Medical Complete (Alumni) ProQuest Central (Alumni Edition) SciTech Premium Collection ProQuest One Community College ProQuest One Health & Nursing ProQuest Natural Science Collection ProQuest Central ProQuest One Applied & Life Sciences ProQuest Health & Medical Research Collection Health Research Premium Collection Health and Medicine Complete (Alumni Edition) Natural Science Collection ProQuest Central Korea Health & Medical Research Collection Biological Science Collection ProQuest Central (New) ProQuest Medical Library (Alumni) ProQuest Public Health ProQuest Biological Science Collection ProQuest One Academic Eastern Edition ProQuest Hospital Collection Health Research Premium Collection (Alumni) Biological Science Database ProQuest SciTech Collection ProQuest Hospital Collection (Alumni) ProQuest Health & Medical Complete ProQuest Medical Library ProQuest One Academic UKI Edition ProQuest One Academic ProQuest One Academic (New) ProQuest Central (Alumni) MEDLINE - Academic
DatabaseTitleList	MEDLINE - Academic Publicly Available Content Database MEDLINE
Database_xml	– sequence: 1 dbid: DOA name: DOAJ Directory of Open Access Journals url: https://www.doaj.org/ sourceTypes: Open Website – sequence: 2 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 3 dbid: PIMPY name: ProQuest Publicly Available Content Database url: http://search.proquest.com/publiccontent sourceTypes: Aggregation Database
DeliveryMethod	fulltext_linktorsrc
Discipline	Biology
EISSN	1664-3224
ExternalDocumentID	oai_doaj_org_article_18c0c593b68d44e59b69ffdbf363a083 PMC11772198 39877358 10_3389_fimmu_2024_1509874
Genre	Journal Article
GroupedDBID	53G 5VS 9T4 AAFWJ AAKDD AAYXX ACGFO ACGFS ADBBV ADRAZ AENEX AFPKN ALMA_UNASSIGNED_HOLDINGS AOIJS BAWUL BCNDV CITATION DIK EBS EMOBN GROUPED_DOAJ GX1 HYE KQ8 M48 M~E OK1 PGMZT RNS RPM ACXDI CGR CUY CVF ECM EIF IPNFZ NPM RIG 3V. 7X7 7XB 88E 8C1 8FE 8FH 8FI 8FJ 8FK ABUWG AFKRA AZQEC BBNVY BENPR BHPHI CCPQU DWQXO FYUFA GNUQQ HCIFZ K9. LK8 M1P M7P PHGZM PHGZT PIMPY PJZUB PKEHL PPXIY PQEST PQGLB PQQKQ PQUKI 7X8 5PM
ID	FETCH-LOGICAL-c497t-bd22c8031043686f99a6bad27c7e21a4868d770c251b9199a1bcb5d1c88124383
IEDL.DBID	M7P
ISICitedReferencesCount	1
ISICitedReferencesURI	http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=001406503900001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
ISSN	1664-3224
IngestDate	Fri Oct 03 12:52:02 EDT 2025 Thu Aug 21 18:40:31 EDT 2025 Thu Sep 04 17:30:23 EDT 2025 Tue Dec 02 16:05:45 EST 2025 Tue May 06 01:31:38 EDT 2025 Sat Nov 29 06:20:13 EST 2025 Tue Nov 18 21:26:48 EST 2025
IsDoiOpenAccess	true
IsOpenAccess	true
IsPeerReviewed	true
IsScholarly	true
Keywords	HIV bryostatin-1 IFN-γ production exhausted CD8+ T cells MAP kinase 11
Language	English
License	Copyright © 2025 Li, Zhao, van Meurs, Brouwers-Haspels, den Dekker, Wilmsen, Grashof, van de Werken, Rao, Rokx, Mueller and Katsikis. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
LinkModel	DirectLink
MergedId	FETCHMERGED-LOGICAL-c497t-bd22c8031043686f99a6bad27c7e21a4868d770c251b9199a1bcb5d1c88124383
Notes	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Edited by: Raquel Alarcon Rodriguez, University of Almeria, Spain Reviewed by: Hiroki Ishikawa, Yasuda Women’s University, Japan Present address: Manzhi Zhao, Department of Pulmonary and Critical Care Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China These authors have contributed equally to this work Kenji Sugata, Kumamoto University, Japan
OpenAccessLink	https://www.proquest.com/docview/3278274005?pq-origsite=%requestingapplication%
PMID	39877358
PQID	3278274005
PQPubID	7426807
ParticipantIDs	doaj_primary_oai_doaj_org_article_18c0c593b68d44e59b69ffdbf363a083 pubmedcentral_primary_oai_pubmedcentral_nih_gov_11772198 proquest_miscellaneous_3160940263 proquest_journals_3278274005 pubmed_primary_39877358 crossref_citationtrail_10_3389_fimmu_2024_1509874 crossref_primary_10_3389_fimmu_2024_1509874
PublicationCentury	2000
PublicationDate	2025-01-14
PublicationDateYYYYMMDD	2025-01-14
PublicationDate_xml	– month: 01 year: 2025 text: 2025-01-14 day: 14
PublicationDecade	2020
PublicationPlace	Switzerland
PublicationPlace_xml	– name: Switzerland – name: Lausanne
PublicationTitle	Frontiers in immunology
PublicationTitleAlternate	Front Immunol
PublicationYear	2025
Publisher	Frontiers Media SA Frontiers Media S.A
Publisher_xml	– name: Frontiers Media SA – name: Frontiers Media S.A
References	Shankar (B62) 2000; 96 Lilly (B76) 1991; 5 Walker-Sperling (B77) 2016; 8 Tuttle (B74) 1992; 52 Raghuvanshi (B15) 2020; 20 Schweneker (B56) 2008; 180 Lecuroux (B69) 2009; 23 MadhuSudan (B24) 2003; 89 Khan (B46) 2019; 571 Marks-Konczalik (B71) 2000; 97 Migueles (B70) 2009; 83 Velu (B41) 2015; 12 Wherry (B48) 2015; 15 Bucks (B1) 2009; 182 Propper (B26) 1998; 78 Díaz (B30) 2015; 5 Ariza (B12) 2011; 286 Tuttle (B21) 1992; 12 Hany (B34) 2022; 96 Philip (B66) 1993; 85 Chin (B19) 2001; 98 Trautmann (B36) 2006; 12 Zhao (B39) 2020; 16 Jones (B18) 1990; 75 Eriksson (B59) 2013; 9 Laird (B63) 2015; 125 Brockstein (B28) 2001; 19 Hess (B53) 1988; 141 Bosco (B65) 1997; 89 Rehr (B68) 2008; 82 Ewels (B84) 2020; 38 Merritt (B49) 2000; 20 Hardman (B10) 2020; 11 Kos (B55) 2000; 22 Kortmansky (B8) 2003; 21 Gutierrez (B32) 2016; 30 Wang (B43) 2019; 10 Lee (B11) 1996; 271 Tuttle (B22) 1992; 52 Jones (B61) 2016; 126 Jayson (B14) 1995; 72 Hofmann (B80) 2004; 316 Alfei (B47) 2019; 571 Hess (B40) 1991; 51 Curiel (B51) 2001; 167 Kollár (B29) 2014; 52 Bui (B7) 2015; 29 Mehla (B31) 2010; 5 Escobar (B44) 2020; 5 Salerno (B79) 2017; 114 Schietinger (B3) 2016; 45 Pagliaro (B25) 2000; 89 Di Tommaso (B85) 2017; 35 Hossain (B6) 2021; 41 Chin (B23) 2004; 16 Strain (B58) 2005; 191 Matthews (B13) 1997; 272 Day (B37) 2006; 443 Crawley (B82) 1997; 272 Esa (B20) 1990; 12 Cook (B50) 2007; 4 Galron (B54) 1994; 158 Le (B73) 2009; 58 Sun (B9) 2006; 12 Steube (B17) 1993; 9 Wherry (B4) 2011; 12 Conze (B83) 2000; 37 Soneson (B86) 2015; 4 Zhang (B81) 1999; 162 Zhao (B35) 2019; 139 Love (B87) 2014; 15 Chun (B60) 1997; 387 Perez (B64) 2010; 8 Utzschneider (B2) 2016; 213 Zonder (B52) 1999; 8 Gubser (B5) 2022; 76 Siddiqui (B45) 2019; 50 Bengsch (B88) 2018; 48 Steube (B78) 1995; 214 Homung (B16) 1992; 52 Quigley (B67) 2010; 16 Miller (B89) 2019; 20 Fenwick (B38) 2019; 292 Macatangay (B42) 2020; 34 Kmieciak (B75) 2011; 47 Gonzalez (B27) 1999; 9 Sengupta (B33) 2018; 48 Li (B72) 2004; 279 Finzi (B57) 1997; 278
References_xml	– volume: 89 year: 2000 ident: B25 article-title: A Phase II trial of bryostatin-1 for patients with metastatic renal cell carcinoma publication-title: Cancer doi: 10.1002/1097-0142(20000801)89:3<615::AID-CNCR17>3.0.CO;2-J – volume: 89 year: 1997 ident: B65 article-title: The antineoplastic agent bryostatin-1 induces proinflammatory cytokine production in human monocytes: synergy with interleukin-2 and modulation of interleukin-2Rγ chain expression publication-title: Blood J Am Soc Hematol doi: 10.1182/blood.V89.9.3402 – volume: 85 year: 1993 ident: B66 article-title: Phase I study of bryostatin 1: assessment of interleukin 6 and tumor necrosis factor alpha induction in vivo. The Cancer Research Campaign Phase I Committee publication-title: J Natl Cancer Inst doi: 10.1093/jnci/85.22.1812 – volume: 4 start-page: 1521 year: 2015 ident: B86 article-title: Differential analyses for RNA-seq: transcript-level estimates improve gene-level inferences publication-title: F1000Res doi: 10.12688/f1000research – volume: 10 year: 2019 ident: B43 article-title: The transcription factor TCF1 preserves the effector function of exhausted CD8 T cells during chronic viral infection publication-title: Front Immunol doi: 10.3389/fimmu.2019.00169 – volume: 162 year: 1999 ident: B81 article-title: p38 mitogen-activated protein kinase mediates signal integration of TCR/CD28 costimulation in primary murine T cells publication-title: J Immunol doi: 10.4049/jimmunol.162.7.3819 – volume: 272 year: 1997 ident: B82 article-title: T cell proliferation in response to interleukins 2 and 7 requires p38MAP kinase activation publication-title: J Biol Chem doi: 10.1074/jbc.272.23.15023 – volume: 50 start-page: 195 year: 2019 ident: B45 article-title: Intratumoral tcf1(+)PD-1(+)CD8(+) T cells with stem-like properties promote tumor control in response to vaccination and checkpoint blockade immunotherapy publication-title: Immunity doi: 10.1016/j.immuni.2018.12.021 – volume: 83 year: 2009 ident: B70 article-title: Defective human immunodeficiency virus-specific CD8+ T-cell polyfunctionality, proliferation, and cytotoxicity are not restored by antiretroviral therapy publication-title: J Virol doi: 10.1128/JVI.01153-09 – volume: 12 year: 2011 ident: B4 article-title: T cell exhaustion publication-title: Nat Immunol doi: 10.1038/ni.2035 – volume: 15 year: 2015 ident: B48 article-title: Molecular and cellular insights into T cell exhaustion publication-title: Nat Rev Immunol doi: 10.1038/nri3862 – volume: 8 year: 1999 ident: B52 article-title: Pharmacology and clinical experience with bryostatin 1: a novel anticancer drug publication-title: Expert Opin Investigational Drugs doi: 10.1517/13543784.8.12.2189 – volume: 75 year: 1990 ident: B18 article-title: Bryostatin 1, a unique biologic response modifier: anti-leukemic activity in vitro publication-title: Blood doi: 10.1182/blood.V75.6.1319.1319 – volume: 571 year: 2019 ident: B47 article-title: TOX reinforces the phenotype and longevity of exhausted T cells in chronic viral infection publication-title: Nature doi: 10.1038/s41586-019-1326-9 – volume: 11 start-page: 1879 year: 2020 ident: B10 article-title: Synthesis and evaluation of designed PKC modulators for enhanced cancer immunotherapy publication-title: Nat Commun doi: 10.1038/s41467-020-15742-7 – volume: 278 year: 1997 ident: B57 article-title: Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy publication-title: Science doi: 10.1126/science.278.5341.1295 – volume: 82 year: 2008 ident: B68 article-title: Emergence of polyfunctional CD8+ T cells after prolonged suppression of human immunodeficiency virus replication by antiretroviral therapy publication-title: J Virol doi: 10.1128/JVI.02383-07 – volume: 30 year: 2016 ident: B32 article-title: Bryostatin-1 for latent virus reactivation in HIV-infected patients on antiretroviral therapy publication-title: AIDS doi: 10.1097/QAD.0000000000001064 – volume: 22 year: 2000 ident: B55 article-title: Protective role of IL-2 during activation of T cells with bryostatin 1 publication-title: Int J Immunopharmacol doi: 10.1016/S0192-0561(00)00027-8 – volume: 8 year: 2016 ident: B77 article-title: The effect of latency reversal agents on primary CD8+ T cells: implications for shock and kill strategies for human immunodeficiency virus eradication publication-title: EBioMedicine doi: 10.1016/j.ebiom.2016.04.019 – volume: 180 year: 2008 ident: B56 article-title: HIV-induced changes in T cell signaling pathways publication-title: J Immunol doi: 10.4049/jimmunol.180.10.6490 – volume: 158 start-page: 195 year: 1994 ident: B54 article-title: Inhibition of PMA-induced human T cell proliferation by bryostatin is associated with enhanced degradation of conventional protein kinase C (cPKC): Ca2+ signals restore mitogenic activity without abrogating enhanced cPKC degradation publication-title: Cell Immunol doi: 10.1006/cimm.1994.1267 – volume: 52 year: 2014 ident: B29 article-title: Marine natural products: Bryostatins in preclinical and clinical studies publication-title: Pharm Biol doi: 10.3109/13880209.2013.804100 – volume: 23 year: 2009 ident: B69 article-title: Antiretroviral therapy initiation during primary HIV infection enhances both CD127 expression and the proliferative capacity of HIV-specific CD8+ T cells publication-title: AIDS doi: 10.1097/QAD.0b013e32832e6634 – volume: 213 year: 2016 ident: B2 article-title: High antigen levels induce an exhausted phenotype in a chronic infection without impairing T cell expansion and survival publication-title: J Exp Med doi: 10.1084/jem.20150598 – volume: 5 start-page: 12442 year: 2015 ident: B30 article-title: Bryostatin activates HIV-1 latent expression in human astrocytes through a PKC and NF-ĸB-dependent mechanism publication-title: Sci Rep doi: 10.1038/srep12442 – volume: 12 year: 2006 ident: B36 article-title: Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction publication-title: Nat Med doi: 10.1038/nm1482 – volume: 125 year: 2015 ident: B63 article-title: Ex vivo analysis identifies effective HIV-1 latency-reversing drug combinations publication-title: J Clin Invest doi: 10.1172/JCI80142 – volume: 72 year: 1995 ident: B14 article-title: A phase I trial of bryostatin 1 in patients with advanced Malignancy using a 24 hour intravenous infusion publication-title: Br J Cancer doi: 10.1038/bjc.1995.356 – volume: 47 start-page: 2381 year: 2011 ident: B75 article-title: Ex vivo expansion of tumor-reactive T cells by means of bryostatin 1/ionomycin and the common gamma chain cytokines formulation publication-title: J Vis Exp doi: 10.3791/2381 – volume: 20 year: 2000 ident: B49 article-title: Activation of p38 mitogen-activated protein kinase in vivo selectively induces apoptosis of CD8+ but not CD4+ T cells publication-title: Mol Cell Biol doi: 10.1128/MCB.20.3.936-946.2000 – volume: 48 year: 2018 ident: B33 article-title: Targeting the latent reservoir for HIV-1 publication-title: Immunity doi: 10.1016/j.immuni.2018.04.030 – volume: 9 start-page: 599 year: 1999 ident: B27 article-title: Treatment of patients with metastatic melanoma with bryostatin-1–a phase II study publication-title: Melanoma Res doi: 10.1097/00008390-199912000-00010 – volume: 12 year: 1990 ident: B20 article-title: Activation of T-cells by bryostatins: induction of the IL-2 receptor gene transcription and down-modulation of surface receptors publication-title: Int J Immunopharmacol doi: 10.1016/0192-0561(90)90110-9 – volume: 8 year: 2010 ident: B64 article-title: Bryostatin-1 synergizes with histone deacetylase inhibitors to reactivate HIV-1 from latency publication-title: Curr HIV Res doi: 10.2174/157016210793499312 – volume: 96 year: 2000 ident: B62 article-title: Impaired function of circulating HIV-specific CD8+ T cells in chronic human immunodeficiency virus infection publication-title: Blood J Am Soc Hematol doi: 10.1182/blood.V96.9.3094 – volume: 571 year: 2019 ident: B46 article-title: TOX transcriptionally and epigenetically programs CD8+ T cell exhaustion publication-title: Nature doi: 10.1038/s41586-019-1325-x – volume: 182 year: 2009 ident: B1 article-title: Chronic antigen stimulation alone is sufficient to drive CD8+ T cell exhaustion publication-title: J Immunol doi: 10.4049/jimmunol.0800997 – volume: 21 year: 2003 ident: B8 article-title: Bryostatin-1: a novel PKC inhibitor in clinical development publication-title: Cancer Invest doi: 10.1081/CNV-120025095 – volume: 214 year: 1995 ident: B78 article-title: The protein kinase C activator Bryostatin-1 induces the rapid release of TNF alpha from MONO-MAC-6 cells publication-title: Biochem Biophys Res Commun doi: 10.1006/bbrc.1995.2413 – volume: 114 year: 2017 ident: B79 article-title: Distinct PKC-mediated posttranscriptional events set cytokine production kinetics in CD8+ T cells publication-title: Proc Natl Acad Sci doi: 10.1073/pnas.1704227114 – volume: 15 start-page: 550 year: 2014 ident: B87 article-title: Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2 publication-title: Genome Biol doi: 10.1186/s13059-014-0550-8 – volume: 48 start-page: 1029 year: 2018 ident: B88 article-title: Epigenomic-guided mass cytometry profiling reveals disease-specific features of exhausted CD8 T cells publication-title: Immunity doi: 10.1016/j.immuni.2018.04.026 – volume: 279 year: 2004 ident: B72 article-title: Interleukin-7 inactivates the pro-apoptotic protein Bad promoting T cell survival publication-title: J Biol Chem doi: 10.1074/jbc.M401656200 – volume: 271 year: 1996 ident: B11 article-title: Dephosphorylation of activated protein kinase C contributes to downregulation by bryostatin publication-title: Am J Physiol doi: 10.1152/ajpcell.1996.271.1.C304 – volume: 387 year: 1997 ident: B60 article-title: Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection publication-title: Nature doi: 10.1038/387183a0 – volume: 19 year: 2001 ident: B28 article-title: Phase II studies of bryostatin-1 in patients with advanced sarcoma and advanced head and neck cancer publication-title: Invest New Drugs doi: 10.1023/A:1010628903248 – volume: 286 start-page: 24 year: 2011 ident: B12 article-title: Bryostatin-1, a naturally occurring antineoplastic agent, acts as a Toll-like receptor 4 (TLR-4) ligand and induces unique cytokines and chemokines in dendritic cells publication-title: J Biol Chem doi: 10.1074/jbc.M110.135921 – volume: 16 year: 2004 ident: B23 article-title: Bryostatin 1/ionomycin (B/I) ex vivo stimulation preferentially activates L-selectinlow tumor-sensitized lymphocytes publication-title: Int Immunol doi: 10.1093/intimm/dxh130 – volume: 16 year: 2010 ident: B67 article-title: Transcriptional analysis of HIV-specific CD8+ T cells shows that PD-1 inhibits T cell function by upregulating BATF publication-title: Nat Med doi: 10.1038/nm.2232 – volume: 5 year: 1991 ident: B76 article-title: Bryostatin 1: a potential anti-leukemic agent for chronic myelomonocytic leukemia publication-title: Leukemia – volume: 126 year: 2016 ident: B61 article-title: HIV-specific CD8+ T cells and HIV eradication publication-title: J Clin Invest doi: 10.1172/JCI80566 – volume: 37 year: 2000 ident: B83 article-title: Activation of p38 MAP kinase in T cells facilitates the immune response to the influenza virus publication-title: Mol Immunol doi: 10.1016/S0161-5890(00)00078-X – volume: 52 year: 1992 ident: B16 article-title: Preclinical evaluation of bryostatin as an anticancer agent against several murine tumor cell lines: in vitro versus in vivo activity publication-title: Cancer Res – volume: 20 year: 2020 ident: B15 article-title: Preclinical and clinical studies on bryostatins, A class of marine-derived protein kinase C modulators: A mini-review publication-title: Curr Top Med Chem doi: 10.2174/1568026620666200325110444 – volume: 4 year: 2007 ident: B50 article-title: The role of the p38 pathway in adaptive immunity publication-title: Cell Mol Immunol – volume: 41 start-page: 156 year: 2021 ident: B6 article-title: Reinvigorating exhausted CD8+ cytotoxic T lymphocytes in the tumor microenvironment and current strategies in cancer immunotherapy publication-title: Med Res Rev doi: 10.1002/med.21727 – volume: 29 year: 2015 ident: B7 article-title: Reversal of T-cell exhaustion as a strategy to improve immune control of HIV-1 publication-title: Aids doi: 10.1097/QAD.0000000000000788 – volume: 34 start-page: 15 year: 2020 ident: B42 article-title: T cells with high PD-1 expression are associated with lower HIV-specific immune responses despite long-term antiretroviral therapy publication-title: AIDS doi: 10.1097/QAD.0000000000002406 – volume: 89 year: 2003 ident: B24 article-title: A multicentre phase II trial of bryostatin-1 in patients with advanced renal cancer publication-title: Br J Cancer doi: 10.1038/sj.bjc.6601321 – volume: 12 start-page: 75 year: 1992 ident: B21 article-title: Bryostatin 1 activates T cells that have antitumor activity publication-title: J Immunother doi: 10.1097/00002371-199208000-00001 – volume: 167 year: 2001 ident: B51 article-title: Bryostatin-1 and IL-2 synergize to induce IFN-γ expression in human peripheral blood T cells: implications for cancer immunotherapy publication-title: J Immunol doi: 10.4049/jimmunol.167.9.4828 – volume: 316 year: 2004 ident: B80 article-title: Mechanical pressure-induced phosphorylation of p38 mitogen-activated protein kinase in epithelial cells via Src and protein kinase C publication-title: Biochem Biophys Res Commun doi: 10.1016/j.bbrc.2004.02.101 – volume: 5 start-page: eabb9726 year: 2020 ident: B44 article-title: T cell factor 1: A master regulator of the T cell response in disease publication-title: Sci Immunol doi: 10.1126/sciimmunol.abb9726 – volume: 139 year: 2019 ident: B35 article-title: T cell toxicity of HIV latency reversing agents publication-title: Pharmacol Res doi: 10.1016/j.phrs.2018.10.023 – volume: 38 year: 2020 ident: B84 article-title: The nf-core framework for community-curated bioinformatics pipelines publication-title: Nat Biotechnol doi: 10.1038/s41587-020-0439-x – volume: 292 year: 2019 ident: B38 article-title: T-cell exhaustion in HIV infection publication-title: Immunol Rev doi: 10.1111/imr.v292.1 – volume: 9 start-page: e1003174 year: 2013 ident: B59 article-title: Comparative analysis of measures of viral reservoirs in HIV-1 eradication studies publication-title: PloS Pathog doi: 10.1371/journal.ppat.1003174 – volume: 12 start-page: 14 year: 2015 ident: B41 article-title: Role of PD-1 co-inhibitory pathway in HIV infection and potential therapeutic options publication-title: Retrovirology doi: 10.1186/s12977-015-0144-x – volume: 272 year: 1997 ident: B13 article-title: Bryostatin 1 induces biphasic activation of protein kinase D in intact cells publication-title: J Biol Chem doi: 10.1074/jbc.272.32.20245 – volume: 51 year: 1991 ident: B40 article-title: The effect of the CD28 activation pathway on the immunosuppressive action of cyclosporine publication-title: Transplantation doi: 10.1097/00007890-199106000-00017 – volume: 52 year: 1992 ident: B22 article-title: Bryostatin 1-activated T cells can traffic and mediate tumor regression publication-title: J Surg Res doi: 10.1016/0022-4804(92)90126-K – volume: 96 start-page: e0195321 year: 2022 ident: B34 article-title: Bryostatin-1 decreases HIV-1 infection and viral production in human primary macrophages publication-title: J Virol doi: 10.1128/jvi.01953-21 – volume: 443 year: 2006 ident: B37 article-title: PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression publication-title: Nature doi: 10.1038/nature05115 – volume: 9 year: 1993 ident: B17 article-title: Differentiation and growth modulation of myeloid leukemia cells by the protein kinase C activating agent bryostatin-1 publication-title: Leuk Lymphoma doi: 10.3109/10428199309148517 – volume: 98 year: 2001 ident: B19 article-title: Bryostatin/ionomycin-activated T cells mediate regression of established tumors publication-title: J Surg Res doi: 10.1006/jsre.2001.6181 – volume: 16 start-page: e1008555 year: 2020 ident: B39 article-title: Rapid in vitro generation of bona fide exhausted CD8+ T cells is accompanied by Tcf7 promotor methylation publication-title: PloS Pathogens doi: 10.1371/journal.ppat.1008555 – volume: 12 start-page: 1 year: 2006 ident: B9 article-title: Bryostatin-1: pharmacology and therapeutic potential as a CNS drug publication-title: CNS Drug Rev doi: 10.1111/j.1527-3458.2006.00001.x – volume: 141 year: 1988 ident: B53 article-title: Activation of human T lymphocytes by bryostatin publication-title: J Immunol (Baltimore Md: 1950) doi: 10.4049/jimmunol.141.10.3263 – volume: 20 year: 2019 ident: B89 article-title: Subsets of exhausted CD8(+) T cells differentially mediate tumor control and respond to checkpoint blockade publication-title: Nat Immunol doi: 10.1038/s41590-019-0312-6 – volume: 76 year: 2022 ident: B5 article-title: Immune checkpoint blockade in HIV publication-title: EBioMedicine doi: 10.1016/j.ebiom.2022.103840 – volume: 78 year: 1998 ident: B26 article-title: A phase II study of bryostatin 1 in metastatic Malignant melanoma publication-title: Br J Cancer doi: 10.1038/bjc.1998.680 – volume: 5 start-page: e11160 year: 2010 ident: B31 article-title: Bryostatin modulates latent HIV-1 infection via PKC and AMPK signaling but inhibits acute infection in a receptor independent manner publication-title: PloS One doi: 10.1371/journal.pone.0011160 – volume: 52 year: 1992 ident: B74 article-title: Activation and growth of murine tumor-specific T-cells which have in vivo activity with bryostatin 1 publication-title: Cancer Res – volume: 97 year: 2000 ident: B71 article-title: IL-2-induced activation-induced cell death is inhibited in IL-15 transgenic mice publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.200363097 – volume: 35 year: 2017 ident: B85 article-title: Nextflow enables reproducible computational workflows publication-title: Nat Biotechnol doi: 10.1038/nbt.3820 – volume: 45 start-page: 389 year: 2016 ident: B3 article-title: Tumor-specific T cell dysfunction is a dynamic antigen-driven differentiation program initiated early during tumorigenesis publication-title: Immunity doi: 10.1016/j.immuni.2016.07.011 – volume: 191 year: 2005 ident: B58 article-title: Effect of treatment, during primary infection, on establishment and clearance of cellular reservoirs of HIV-1 publication-title: J Infect Dis doi: 10.1086/jid.2005.191.issue-9 – volume: 58 year: 2009 ident: B73 article-title: Incubation of antigen-sensitized T lymphocytes activated with bryostatin 1 + ionomycin in IL-7 + IL-15 increases yield of cells capable of inducing regression of melanoma metastases compared to culture in IL-2 publication-title: Cancer Immunol Immunother doi: 10.1007/s00262-009-0666-y
SSID	ssj0000493335
Score	2.3985875
Snippet	Bryostatin-1, a potent agonist of the protein kinase C, has been studied for HIV and cancer therapies. In HIV research, it has shown anti-HIV effects during... IntroductionBryostatin-1, a potent agonist of the protein kinase C, has been studied for HIV and cancer therapies. In HIV research, it has shown anti-HIV...
SourceID	doaj pubmedcentral proquest pubmed crossref
SourceType	Open Website Open Access Repository Aggregation Database Index Database Enrichment Source
StartPage	1509874
SubjectTerms	Animals bryostatin-1 Bryostatins - pharmacology Cancer Cancer immunotherapy Cancer therapies CD8 antigen CD8-Positive T-Lymphocytes - drug effects CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - metabolism Cell growth Cell proliferation Cell Proliferation - drug effects Chronic infection Clinical trials Cytotoxicity Down-regulation exhausted CD8+ T cells Flow cytometry Hepatocyte nuclear factor 1 HIV HIV Infections - drug therapy HIV Infections - immunology HIV-1 - immunology Human immunodeficiency virus Humans IFN-γ production Immunity (Disease) Immunology Infections Kinases Lymphocyte Activation - drug effects Lymphocytes Lymphocytes T MAP kinase MAP kinase 11 Mice PD-1 protein Peptides Protein kinase C Proteins Ribonucleic acid RNA Sequence analysis Transcription factors Up-Regulation γ-Interferon
SummonAdditionalLinks	– databaseName: DOAJ Directory of Open Access Journals dbid: DOA link: http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1La9wwEBYltNBL6btukqJCb8HN6mFLOubRUCgNOaSQm9GTdWm8m32E7L_PjOUsu6W0lx5tyWY8M9J8I0vfEPKJJyucsFUpKxZLqZwsHYPLWiqrguTJsdAXm1Dn5_rqylxslPrCPWGZHjgr7pBpP_KVEa7WQcpYGVeblIJLohYW8APOvoB6NpKpnxn3CiGqfEoGsjBzmNrr6yXkg1x-BgwEmbbcikQ9Yf-fUObvmyU3os_Zc_JsgI30KIv7gjyK3UvyJBeSXL0iN8ez1QTPBrVdyWjsxmjLOQVwR6dYlifFbGhqu0AxlOUVQEDgdJJovBsj-08M9ORUH9BLiqv5c-pWdDmd5Vr1EODo96ML-q3tIOxRxl6TH2dfLk--lkMxhdJLoxalC5x7jUSgyDlfJ2Ns7WzgyqvImZUa9KvUyAPecYZBK3PeVYF5jRAA8tg3ZKebdPEdoUZVCV7nghVSCu5NgLyttjFYx6NPriDsQbGNH5jGseDFrwYyDjRG0xujQWM0gzEKcrB-Zpp5Nv7a-xjtte6JHNn9DfCcZvCc5l-eU5C9B2s3w8CdN4IDZFIwsVUF-bhuhiGHmrddnCyhD6uRdZDX8Iq32TnWkggQT4lKF0Rvuc2WqNstXTvuab3x9znED_3-f3zcLnnKsVLxiJVM7pGdxWwZ98ljf7to57MP_WC5BxqcGi4 priority: 102 providerName: Directory of Open Access Journals
Title	Bryostatin-1 enhances the proliferation and functionality of exhausted CD8+ T cells by upregulating MAP Kinase 11
URI	https://www.ncbi.nlm.nih.gov/pubmed/39877358 https://www.proquest.com/docview/3278274005 https://www.proquest.com/docview/3160940263 https://pubmed.ncbi.nlm.nih.gov/PMC11772198 https://doaj.org/article/18c0c593b68d44e59b69ffdbf363a083
Volume	15
WOSCitedRecordID	wos001406503900001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
hasFullText	1
inHoldings	1
isFullTextHit
isPrint
journalDatabaseRights	– providerCode: PRVAON databaseName: DOAJ Directory of Open Access Journals customDbUrl: eissn: 1664-3224 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0000493335 issn: 1664-3224 databaseCode: DOA dateStart: 20100101 isFulltext: true titleUrlDefault: https://www.doaj.org/ providerName: Directory of Open Access Journals – providerCode: PRVHPJ databaseName: ROAD: Directory of Open Access Scholarly Resources customDbUrl: eissn: 1664-3224 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0000493335 issn: 1664-3224 databaseCode: M~E dateStart: 20100101 isFulltext: true titleUrlDefault: https://road.issn.org providerName: ISSN International Centre
link	http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1Lb9NAEF7RFiQu5U0DJVokbpVp9mHv-oSakAqEGlmoSOFk7ctNJGqneSBy4bczYzuBINQLl5XsXVtjz6znsevvI-QNL4ywwsSRjFmIpLIysgwOE6mM8pIXlvmabEKNRno8TrO24LZot1Vuvon1h9pXDmvkp4KDL1NgcfG72U2ErFG4utpSaOyRA0RJEPXWvWxbY4HoVwgRN__KQC6WnhbT6-sVZIVcvoVICPJtueOPatj-f8Waf2-Z_MMHnT_4X-kfksM2-qRnjbk8IndC-Zjca_go10_ITX--rvAXo2kZMRrKCZrEgkKMSGfI7lOExl6oKT1Fj9gUEiGQp1VBw48JgggFTwfv9Qm9pLgosKB2TVezeUN5D36SXpxl9NO0BO9JGXtKvpwPLwcfopaTIXIyVcvIes6dRjxRhK5PijQ1iTWeK6cCZ0bqRHuleg7CJpsy6GXW2dgzpzGSgHT4GdkvqzIcEZqquIDbWW-ElIK71EP6l5jgjeXBFbZD2EYzuWsBy5E341sOiQtqM6-1maM281abHXKyvWbWwHXcOrqPCt-ORKjt-kQ1v8rbmZsz7XouToWFJ5MyxKlN0qLwthCJMBDAdsjxRuV5O_8X-W99d8jrbTfMXHzzpgzVCsawBMELeQK3eN5Y11YSAeIpEesO0Tt2tyPqbk85ndTo4LgKD25Iv7hdrpfkPkcq4x6LmDwm-8v5Krwid9335XQx75I9NVZ1q6HVA9YlB_3hKPvcrYsW3XqeYftzCD3Zx4vs6y9tIjAV
linkProvider	ProQuest
linkToHtml	http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMw1V1JbxMxFLZKCoIL-xIoYCQ4VUPjZcb2AaEuVI3SRDkEqZym3iaJRGfSLED-FL-R55lJIAj11gPHGXss2_O9zcv7EHpLM80M03HEY-IjLgyPDIHHhAstHKeZIa4kmxC9njw7U_0t9HN1FyYcq1zpxFJRu8KGNfI9RsGWCUBc_HFyGQXWqLC7uqLQqGDR8cvvELLNPrSP4P--o_T40-DwJKpZBSLLlZhHxlFqZciIGZKvJ5lSOjHaUWGFp0RzmUgnRMuC4TeKQCkx1sSOWBlsIQR00O4NtM0B7LKBtvvtbv_LelUH_G3GWFzdzoHoT-1l44uLBcShlL8H3wsifL5hAUuigH95t38f0vzD6h3f-9_m6z66W_vXeL8SiAdoy-cP0a2KcXP5CF0eTJdFuEQ1ziOCfT4KoJ9h8ILxJPAXZb6SCKxzh4PNr5ZKIVTBRYb9j1FIk-QdPjySu3iAw7bHDJslXkymflgyoeVD3N3v4844B_8AE_IYfb6W8T5BjbzI_TOElYgzaM44zThn1CoHAW6ivdOGepuZJiIrJKS2TskemEG-phCaBfSkJXrSgJ60Rk8T7a6_mVQJSa6sfRAAtq4ZkomXL4rpMK11U0qkbdlYMQMj49zHyiQqy5zJWMI0uOhNtLOCWFpruFn6G19N9GZdDLopzLzOfbGAOiQJ6RlpAk08rdC87gmD7gkWyyaSGzjf6OpmST4elfnPwzkDMLTy-dX9eo1unwy6p-lpu9d5ge7QQNzcIhHhO6gxny78S3TTfpuPZ9NXtRRjdH7dgvALKWKD9w
openUrl	ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Bryostatin-1+enhances+the+proliferation+and+functionality+of+exhausted+CD8%2B+T+cells+by+upregulating+MAP+Kinase+11&rft.jtitle=Frontiers+in+immunology&rft.au=Li%2C+Ling&rft.au=Zhao%2C+Manzhi&rft.au=Marjan+van+Meurs&rft.au=Brouwers-Haspels%2C+Inge&rft.date=2025-01-14&rft.pub=Frontiers+Media+SA&rft.eissn=1664-3224&rft.volume=15&rft.spage=1509874&rft_id=info:doi/10.3389%2Ffimmu.2024.1509874
thumbnail_l	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1664-3224&client=summon
thumbnail_m	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1664-3224&client=summon
thumbnail_s	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1664-3224&client=summon