Subcutaneous checkpoint inhibition is equivalent to systemic delivery when combined with nelitolimod delivered via pressure-enabled drug delivery for depletion of intrahepatic myeloid-derived suppressor cells and control of liver metastases

BackgroundToll-like receptor 9 (TLR9) agonists induce inflammatory responses that promote the killing of infectious micro-organisms, cancer cells and develop adaptive immune responses. Their ability as immunomodulators to enhance the activity of checkpoint inhibitors (CPI) in treating liver tumors i...

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Published in:Journal for immunotherapy of cancer Vol. 12; no. 7; p. e008837
Main Authors: Ghosh, Chandra C, Cournoyer, Lauren, Liu, Yujia, Ballarin, Alizee, Layman, Ilan B, LaPorte, Jason, Morrissey, Molly, Fraser, Kayla, Perati, Shriya, Cox, Bryan F, Yakirevich, Evgeny, Treaba, Diana O, Murtha, Timothy D, Guha, Prajna, Katz, Steven C, Davar, Diwakar
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Language:English
Published: England BMJ Publishing Group Ltd 22.07.2024
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ISSN:2051-1426, 2051-1426
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Abstract BackgroundToll-like receptor 9 (TLR9) agonists induce inflammatory responses that promote the killing of infectious micro-organisms, cancer cells and develop adaptive immune responses. Their ability as immunomodulators to enhance the activity of checkpoint inhibitors (CPI) in treating liver tumors is limited in part by the distinctive biology of intrahepatic myeloid-derived suppressor cells (MDSC) and challenges with tumor-specific therapeutic delivery. We have shown that the regional delivery of type C TLR9 agonist via pressure-enabled drug delivery (PEDD) system improves delivery to the tumor, enhances depletion of MDSCs and overall, stimulates the immune system in combination with or without CPI. Currently, CPIs are delivered intravenously, although there is a growing interest in its subcutaneous (SQ) administration. We compared nelitolimod formerly known as SD-101 administered using PEDD in combination with systemic (Sys) or SQ CPI in murine liver metastases (LM).MethodsThe LM model was developed by injecting MC38-Luc cells via the spleen of 8–12 week old male C57/BL6 mice followed by splenectomy. After a week, fluorescently labeled nelitolimod (10 µg/mouse) was delivered via PEDD and co-administered anti-programmed cell death-1 (α-PD-1) either via Sys or SQ. Tumor burden was monitored by in vivo imaging system. Serum cytokine levels were analyzed by Luminex. Tissues were harvested on Day 3 (D3) or Day 10 (D10) post-PEDD to enrich CD45+ cells and were analyzed via NanoString targeted transcriptomics (D3) or flow cytometry (FC, D10) to interrogate immune cell populations (D10). For NanoString analysis, the innate immune panels were selected, and for FC, MDSCs (CD11b+Gr1+), B cells (B220+), dendritic cells (DC, CD11c+), T (CD3+) cells, and M1-like macrophages (F4/80+CD38+Egr2−) were quantified.ResultsNelitolimod delivered via PEDD resulted in changes in innate and adaptive immune cells within LM, including depletion of liver MDSC and increased M1-like macrophages in the liver, which are supportive of antitumor immunity. While CPI monotherapy failed to control tumor progression, nelitolimod and CPI combination improved LM control, survival and antitumor immunity beyond the nelitolimod monotherapy effect, irrespective of CPI delivery route.ConclusionThe SQ route of CPI delivery was equivalent to Sys in combination with nelitolimod, suggesting SQ-CPI may be a rational choice in combination with PEDD of nelitolimod for liver tumor treatment.
AbstractList Toll-like receptor 9 (TLR9) agonists induce inflammatory responses that promote the killing of infectious micro-organisms, cancer cells and develop adaptive immune responses. Their ability as immunomodulators to enhance the activity of checkpoint inhibitors (CPI) in treating liver tumors is limited in part by the distinctive biology of intrahepatic myeloid-derived suppressor cells (MDSC) and challenges with tumor-specific therapeutic delivery. We have shown that the regional delivery of type C TLR9 agonist via pressure-enabled drug delivery (PEDD) system improves delivery to the tumor, enhances depletion of MDSCs and overall, stimulates the immune system in combination with or without CPI. Currently, CPIs are delivered intravenously, although there is a growing interest in its subcutaneous (SQ) administration. We compared nelitolimod formerly known as SD-101 administered using PEDD in combination with systemic (Sys) or SQ CPI in murine liver metastases (LM).BACKGROUNDToll-like receptor 9 (TLR9) agonists induce inflammatory responses that promote the killing of infectious micro-organisms, cancer cells and develop adaptive immune responses. Their ability as immunomodulators to enhance the activity of checkpoint inhibitors (CPI) in treating liver tumors is limited in part by the distinctive biology of intrahepatic myeloid-derived suppressor cells (MDSC) and challenges with tumor-specific therapeutic delivery. We have shown that the regional delivery of type C TLR9 agonist via pressure-enabled drug delivery (PEDD) system improves delivery to the tumor, enhances depletion of MDSCs and overall, stimulates the immune system in combination with or without CPI. Currently, CPIs are delivered intravenously, although there is a growing interest in its subcutaneous (SQ) administration. We compared nelitolimod formerly known as SD-101 administered using PEDD in combination with systemic (Sys) or SQ CPI in murine liver metastases (LM).The LM model was developed by injecting MC38-Luc cells via the spleen of 8-12 week old male C57/BL6 mice followed by splenectomy. After a week, fluorescently labeled nelitolimod (10 µg/mouse) was delivered via PEDD and co-administered anti-programmed cell death-1 (α-PD-1) either via Sys or SQ. Tumor burden was monitored by in vivo imaging system. Serum cytokine levels were analyzed by Luminex. Tissues were harvested on Day 3 (D3) or Day 10 (D10) post-PEDD to enrich CD45+ cells and were analyzed via NanoString targeted transcriptomics (D3) or flow cytometry (FC, D10) to interrogate immune cell populations (D10). For NanoString analysis, the innate immune panels were selected, and for FC, MDSCs (CD11b+Gr1+), B cells (B220+), dendritic cells (DC, CD11c+), T (CD3+) cells, and M1-like macrophages (F4/80+CD38+Egr2-) were quantified.METHODSThe LM model was developed by injecting MC38-Luc cells via the spleen of 8-12 week old male C57/BL6 mice followed by splenectomy. After a week, fluorescently labeled nelitolimod (10 µg/mouse) was delivered via PEDD and co-administered anti-programmed cell death-1 (α-PD-1) either via Sys or SQ. Tumor burden was monitored by in vivo imaging system. Serum cytokine levels were analyzed by Luminex. Tissues were harvested on Day 3 (D3) or Day 10 (D10) post-PEDD to enrich CD45+ cells and were analyzed via NanoString targeted transcriptomics (D3) or flow cytometry (FC, D10) to interrogate immune cell populations (D10). For NanoString analysis, the innate immune panels were selected, and for FC, MDSCs (CD11b+Gr1+), B cells (B220+), dendritic cells (DC, CD11c+), T (CD3+) cells, and M1-like macrophages (F4/80+CD38+Egr2-) were quantified.Nelitolimod delivered via PEDD resulted in changes in innate and adaptive immune cells within LM, including depletion of liver MDSC and increased M1-like macrophages in the liver, which are supportive of antitumor immunity. While CPI monotherapy failed to control tumor progression, nelitolimod and CPI combination improved LM control, survival and antitumor immunity beyond the nelitolimod monotherapy effect, irrespective of CPI delivery route.RESULTSNelitolimod delivered via PEDD resulted in changes in innate and adaptive immune cells within LM, including depletion of liver MDSC and increased M1-like macrophages in the liver, which are supportive of antitumor immunity. While CPI monotherapy failed to control tumor progression, nelitolimod and CPI combination improved LM control, survival and antitumor immunity beyond the nelitolimod monotherapy effect, irrespective of CPI delivery route.The SQ route of CPI delivery was equivalent to Sys in combination with nelitolimod, suggesting SQ-CPI may be a rational choice in combination with PEDD of nelitolimod for liver tumor treatment.CONCLUSIONThe SQ route of CPI delivery was equivalent to Sys in combination with nelitolimod, suggesting SQ-CPI may be a rational choice in combination with PEDD of nelitolimod for liver tumor treatment.
Toll-like receptor 9 (TLR9) agonists induce inflammatory responses that promote the killing of infectious micro-organisms, cancer cells and develop adaptive immune responses. Their ability as immunomodulators to enhance the activity of checkpoint inhibitors (CPI) in treating liver tumors is limited in part by the distinctive biology of intrahepatic myeloid-derived suppressor cells (MDSC) and challenges with tumor-specific therapeutic delivery. We have shown that the regional delivery of type C TLR9 agonist via pressure-enabled drug delivery (PEDD) system improves delivery to the tumor, enhances depletion of MDSCs and overall, stimulates the immune system in combination with or without CPI. Currently, CPIs are delivered intravenously, although there is a growing interest in its subcutaneous (SQ) administration. We compared nelitolimod formerly known as SD-101 administered using PEDD in combination with systemic (Sys) or SQ CPI in murine liver metastases (LM). The LM model was developed by injecting MC38-Luc cells via the spleen of 8-12 week old male C57/BL6 mice followed by splenectomy. After a week, fluorescently labeled nelitolimod (10 µg/mouse) was delivered via PEDD and co-administered anti-programmed cell death-1 (α-PD-1) either via Sys or SQ. Tumor burden was monitored by in vivo imaging system. Serum cytokine levels were analyzed by Luminex. Tissues were harvested on Day 3 (D3) or Day 10 (D10) post-PEDD to enrich CD45 cells and were analyzed via NanoString targeted transcriptomics (D3) or flow cytometry (FC, D10) to interrogate immune cell populations (D10). For NanoString analysis, the innate immune panels were selected, and for FC, MDSCs (CD11b Gr1 ), B cells (B220 ), dendritic cells (DC, CD11c ), T (CD3 ) cells, and M1-like macrophages (F4/80 CD38 Egr2 ) were quantified. Nelitolimod delivered via PEDD resulted in changes in innate and adaptive immune cells within LM, including depletion of liver MDSC and increased M1-like macrophages in the liver, which are supportive of antitumor immunity. While CPI monotherapy failed to control tumor progression, nelitolimod and CPI combination improved LM control, survival and antitumor immunity beyond the nelitolimod monotherapy effect, irrespective of CPI delivery route. The SQ route of CPI delivery was equivalent to Sys in combination with nelitolimod, suggesting SQ-CPI may be a rational choice in combination with PEDD of nelitolimod for liver tumor treatment.
Background Toll-like receptor 9 (TLR9) agonists induce inflammatory responses that promote the killing of infectious micro-organisms, cancer cells and develop adaptive immune responses. Their ability as immunomodulators to enhance the activity of checkpoint inhibitors (CPI) in treating liver tumors is limited in part by the distinctive biology of intrahepatic myeloid-derived suppressor cells (MDSC) and challenges with tumor-specific therapeutic delivery. We have shown that the regional delivery of type C TLR9 agonist via pressure-enabled drug delivery (PEDD) system improves delivery to the tumor, enhances depletion of MDSCs and overall, stimulates the immune system in combination with or without CPI. Currently, CPIs are delivered intravenously, although there is a growing interest in its subcutaneous (SQ) administration. We compared nelitolimod formerly known as SD-101 administered using PEDD in combination with systemic (Sys) or SQ CPI in murine liver metastases (LM).Methods The LM model was developed by injecting MC38-Luc cells via the spleen of 8–12 week old male C57/BL6 mice followed by splenectomy. After a week, fluorescently labeled nelitolimod (10 µg/mouse) was delivered via PEDD and co-administered anti-programmed cell death-1 (α-PD-1) either via Sys or SQ. Tumor burden was monitored by in vivo imaging system. Serum cytokine levels were analyzed by Luminex. Tissues were harvested on Day 3 (D3) or Day 10 (D10) post-PEDD to enrich CD45+ cells and were analyzed via NanoString targeted transcriptomics (D3) or flow cytometry (FC, D10) to interrogate immune cell populations (D10). For NanoString analysis, the innate immune panels were selected, and for FC, MDSCs (CD11b+Gr1+), B cells (B220+), dendritic cells (DC, CD11c+), T (CD3+) cells, and M1-like macrophages (F4/80+CD38+Egr2−) were quantified.Results Nelitolimod delivered via PEDD resulted in changes in innate and adaptive immune cells within LM, including depletion of liver MDSC and increased M1-like macrophages in the liver, which are supportive of antitumor immunity. While CPI monotherapy failed to control tumor progression, nelitolimod and CPI combination improved LM control, survival and antitumor immunity beyond the nelitolimod monotherapy effect, irrespective of CPI delivery route.Conclusion The SQ route of CPI delivery was equivalent to Sys in combination with nelitolimod, suggesting SQ-CPI may be a rational choice in combination with PEDD of nelitolimod for liver tumor treatment.
BackgroundToll-like receptor 9 (TLR9) agonists induce inflammatory responses that promote the killing of infectious micro-organisms, cancer cells and develop adaptive immune responses. Their ability as immunomodulators to enhance the activity of checkpoint inhibitors (CPI) in treating liver tumors is limited in part by the distinctive biology of intrahepatic myeloid-derived suppressor cells (MDSC) and challenges with tumor-specific therapeutic delivery. We have shown that the regional delivery of type C TLR9 agonist via pressure-enabled drug delivery (PEDD) system improves delivery to the tumor, enhances depletion of MDSCs and overall, stimulates the immune system in combination with or without CPI. Currently, CPIs are delivered intravenously, although there is a growing interest in its subcutaneous (SQ) administration. We compared nelitolimod formerly known as SD-101 administered using PEDD in combination with systemic (Sys) or SQ CPI in murine liver metastases (LM).MethodsThe LM model was developed by injecting MC38-Luc cells via the spleen of 8–12 week old male C57/BL6 mice followed by splenectomy. After a week, fluorescently labeled nelitolimod (10 µg/mouse) was delivered via PEDD and co-administered anti-programmed cell death-1 (α-PD-1) either via Sys or SQ. Tumor burden was monitored by in vivo imaging system. Serum cytokine levels were analyzed by Luminex. Tissues were harvested on Day 3 (D3) or Day 10 (D10) post-PEDD to enrich CD45+ cells and were analyzed via NanoString targeted transcriptomics (D3) or flow cytometry (FC, D10) to interrogate immune cell populations (D10). For NanoString analysis, the innate immune panels were selected, and for FC, MDSCs (CD11b+Gr1+), B cells (B220+), dendritic cells (DC, CD11c+), T (CD3+) cells, and M1-like macrophages (F4/80+CD38+Egr2−) were quantified.ResultsNelitolimod delivered via PEDD resulted in changes in innate and adaptive immune cells within LM, including depletion of liver MDSC and increased M1-like macrophages in the liver, which are supportive of antitumor immunity. While CPI monotherapy failed to control tumor progression, nelitolimod and CPI combination improved LM control, survival and antitumor immunity beyond the nelitolimod monotherapy effect, irrespective of CPI delivery route.ConclusionThe SQ route of CPI delivery was equivalent to Sys in combination with nelitolimod, suggesting SQ-CPI may be a rational choice in combination with PEDD of nelitolimod for liver tumor treatment.
Author Layman, Ilan B
Cox, Bryan F
Liu, Yujia
Perati, Shriya
Murtha, Timothy D
Morrissey, Molly
Davar, Diwakar
Ballarin, Alizee
Katz, Steven C
Fraser, Kayla
Yakirevich, Evgeny
Guha, Prajna
Treaba, Diana O
Ghosh, Chandra C
Cournoyer, Lauren
LaPorte, Jason
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  organization: Department of Surgery, Brown University School of Medicine, Providence, RI, USA
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  organization: Trisalus Life Sciences, Westminster, Colorado, USA
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  organization: Trisalus Life Sciences, Westminster, Colorado, USA
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  fullname: Cox, Bryan F
  organization: Trisalus Life Sciences, Westminster, Colorado, USA
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  surname: Yakirevich
  fullname: Yakirevich, Evgeny
  organization: Department of Pathology, Brown University School of Medicine, Providence, Rhode Island, USA
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  organization: Department of Pathology, Brown University School of Medicine, Providence, Rhode Island, USA
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  organization: Department of Surgery, Brown University School of Medicine, Providence, RI, USA
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  surname: Davar
  fullname: Davar, Diwakar
  email: davard@upmc.edu
  organization: Department of Hematology and Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA, USA
BackLink https://www.ncbi.nlm.nih.gov/pubmed/39038918$$D View this record in MEDLINE/PubMed
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Cites_doi 10.1093/annonc/mdw685
10.1158/2159-8290.CD-21-0425
10.1158/2159-8290.CD-18-0280
10.1158/1538-7445.AM2023-1858
10.1200/JCO.20.00605
10.2147/DDDT.S267433
10.1172/JCI80011
10.1097/CAD.0000000000000648
10.1172/jci.insight.93433
10.1126/scitranslmed.aad7118
10.1038/s41417-022-00484-z
10.1007/s10120-018-00922-8
10.4049/jimmunol.170.8.4061
10.3389/fimmu.2021.643771
10.1038/s41388-018-0449-z
10.1038/s41573-021-00345-8
10.1016/j.surg.2023.05.011
10.3389/fimmu.2020.00783
10.1172/JCI87324
10.1084/jem.192.7.1027
10.1038/70932
10.1016/j.cellimm.2021.104295
10.1038/s41392-021-00670-9
10.3390/vaccines9080807
10.1136/jitc-2020-001097
10.1007/s10637-022-01287-7
10.1001/jamaoncol.2019.2187
10.1002/cpt.3148
10.1073/pnas.1608555113
10.1007/s12325-017-0610-z
10.1158/2326-6066.CIR-16-0325
10.1371/journal.pone.0157957
10.1038/328267a0
10.1002/cam4.573
10.1200/JCO.20.00550
10.1007/s00262-013-1508-5
10.1007/s40261-023-01254-x
10.1016/j.celrep.2022.111295
10.1001/jamaoncol.2019.0836
10.1038/s41571-019-0218-0
10.1002/onco.13817
10.1007/s40265-023-01884-7
10.4049/jimmunol.1701019
10.1038/s41591-020-1131-x
10.1056/NEJMoa2216334
10.1189/jlb.3A0114-012RR
10.1200/jco.20.00550
10.1136/jitc-2022-SITC2022.1165
10.1136/jitc-2023-SITC2023.1534
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Issue 7
Keywords Myeloid-derived suppressor cell - MDSC
Toll-like receptor - TLR
Immune Checkpoint Inhibitor
Tumor microenvironment - TME
Language English
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CCG, YL, AB, JL, MM, KF, BFC, PG, SCK are employee of Trisalus Life Sciences. LC, IBL, SP, EY, DOT, TM have no conflict of interest. Conflict of interests of DD are: Grants/Research Support (institutional): Arcus, CellSight Technologies, Immunocore, Merck, Regeneron Pharmaceuticals, Tesaro/GSK. Consultant: ACM Bio, Ascendis Pharma, Clinical Care Options (CCO), Gerson Lehrman Group (GLG), Merck, Medical Learning Group (MLG), Xilio Therapeutics. CE Speakers’ Bureau: Castle Biosciences. Intellectual Property: US Patent 63/124,231, “Compositions and Methods for Treating Cancer”, December 11, 2020 US Patent 63/208,719, “Compositions and Methods For Responsiveness to Immune Checkpoint Inhibitors (ICI), Increasing Effectiveness of ICI and Treating Cancer”, June 9, 2021.
SCK and DD are joint senior authors.
Supplement: Additional supplemental material is published online only. To view, please visit the journal online (https://doi.org/10.1136/jitc-2024-008837).
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.
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References Ostrand-Rosenberg, Fenselau (R14) 2018; 200
Ghosh, Heatherton, Connell (R24) 2022; 29
Chai, Hardaway, Heatherton (R49) 2021; 9
Daud, Loo, Pauli (R12) 2016; 126
Topalian, Hodi, Brahmer (R10) 2019; 5
Chen, Han (R41) 2015; 125
Zou, Wolchok, Chen (R4) 2016; 8
Ai, Chen, Yan (R5) 2020; 14
Ma, Zhang, Greten (R45) 2021; 361
Shimizu, Nakajima, Yamamoto (R32) 2022; 40
Rummel, Kim, Aversa (R37) 2017; 28
Blackwell, Krieg (R39) 2003; 170
Ribas, Medina, Kummar (R19) 2018; 8
Guha, Gardell, Darpolor (R43) 2019; 38
Freeman, Long, Iwai (R3) 2000; 192
Davies, Berge, Boehnke (R34) 2017; 34
Ribas, Medina, Kirkwood (R18) 2021; 11
Katz, Moody, Guha (R20) 2020; 8
Tumeh, Hellmann, Hamid (R11) 2017; 5
Hou, Hou, Huang (R15) 2020; 11
Shin, Kumar, Guo (R28) 2023; 43
Johnson, Braiteh, Grilley-Olson (R30) 2019; 5
De Cock, Kritikou, Sandoval (R35) 2016; 11
Yu, Green, Li (R17) 2021; 27
Pelster, Gruschkus, Bassett (R26) 2021; 39
Li, Shi, Zhang (R48) 2021; 6
Kang (R6) 2023; 83
Piulats, Espinosa, de la Cruz Merino (R27) 2021; 39
Wang, Campos, Gallotta (R38) 2016; 113
Loo, Tsai, Mahuron (R13) 2017; 2
Korman, Garrett-Thomson, Lonberg (R8) 2022; 21
Jaroch, Ghosh, Guha (R21) 2023; 83
Papadopoulos, Harb, Peer (R31) 2021; 26
De Cock, Pivot, Hauser (R36) 2016; 5
Thorn, Point, Burga (R46) 2014; 96
Meyer, Cagnon, Costa-Nunes (R16) 2014; 63
Capacio, Shankara Narayanan, Vicente (R22) 2023; 174
Franken, Kanters, Coenen (R29) 2018; 29
Xu, Wei, Feng (R47) 2022; 40
Dong, Zhu, Tamada (R2) 1999; 5
Mirza, Chase, Slomovitz (R7) 2023; 388
Zhao, Sanghavi, Roy (R33) 2024; 115
Martins, Sofiya, Sykiotis (R50) 2019; 16
Mehta, Kadel, Townsend (R23) 2021; 12
Brunet, Denizot, Luciani (R1) 1987; 328
Sasaki, Nakamura, Mishima (R9) 2019; 22
Katz (2025100304432731000_12.7.e008837.20) 2020; 8
Sasaki (2025100304432731000_12.7.e008837.9) 2019; 22
2025100304432731000_12.7.e008837.27
2025100304432731000_12.7.e008837.26
Topalian (2025100304432731000_12.7.e008837.10) 2019; 5
Mirza (2025100304432731000_12.7.e008837.7) 2023; 388
De Cock (2025100304432731000_12.7.e008837.35) 2016; 11
Zhao (2025100304432731000_12.7.e008837.33) 2024; 115
Ghosh (2025100304432731000_12.7.e008837.24) 2022; 29
Xu (2025100304432731000_12.7.e008837.47) 2022; 40
Mehta (2025100304432731000_12.7.e008837.23) 2021; 12
Capacio (2025100304432731000_12.7.e008837.22) 2023; 174
Johnson (2025100304432731000_12.7.e008837.30) 2019; 5
Guha (2025100304432731000_12.7.e008837.43) 2019; 38
2025100304432731000_12.7.e008837.38
2025100304432731000_12.7.e008837.39
2025100304432731000_12.7.e008837.37
Ma (2025100304432731000_12.7.e008837.45) 2021; 361
Franken (2025100304432731000_12.7.e008837.29) 2018; 29
Korman (2025100304432731000_12.7.e008837.8) 2022; 21
Jaroch (2025100304432731000_12.7.e008837.21) 2023; 83
Chai (2025100304432731000_12.7.e008837.49) 2021; 9
2025100304432731000_12.7.e008837.41
2025100304432731000_12.7.e008837.42
2025100304432731000_12.7.e008837.40
Li (2025100304432731000_12.7.e008837.48) 2021; 6
Papadopoulos (2025100304432731000_12.7.e008837.31) 2021; 26
Kang (2025100304432731000_12.7.e008837.6) 2023; 83
2025100304432731000_12.7.e008837.46
2025100304432731000_12.7.e008837.44
2025100304432731000_12.7.e008837.2
Brunet (2025100304432731000_12.7.e008837.1) 1987; 328
Shin (2025100304432731000_12.7.e008837.28) 2023; 43
2025100304432731000_12.7.e008837.50
2025100304432731000_12.7.e008837.3
cr-split#-2025100304432731000_12.7.e008837.25.2
cr-split#-2025100304432731000_12.7.e008837.25.1
Hou (2025100304432731000_12.7.e008837.15) 2020; 11
Zou (2025100304432731000_12.7.e008837.4) 2016; 8
Ai (2025100304432731000_12.7.e008837.5) 2020; 14
De Cock (2025100304432731000_12.7.e008837.36) 2016; 5
Shimizu (2025100304432731000_12.7.e008837.32) 2022; 40
Davies (2025100304432731000_12.7.e008837.34) 2017; 34
2025100304432731000_12.7.e008837.18
2025100304432731000_12.7.e008837.19
2025100304432731000_12.7.e008837.16
2025100304432731000_12.7.e008837.17
2025100304432731000_12.7.e008837.14
2025100304432731000_12.7.e008837.12
2025100304432731000_12.7.e008837.11
Loo (2025100304432731000_12.7.e008837.13) 2017; 2
References_xml – volume: 28
  start-page: 836
  year: 2017
  ident: R37
  article-title: Preference for subcutaneous or intravenous administration of rituximab among patients with untreated Cd20+ diffuse large B-cell lymphoma or follicular lymphoma: results from a prospective, randomized, open-label, crossover study (Prefmab)
  publication-title: Ann Oncol
  doi: 10.1093/annonc/mdw685
– volume: 11
  start-page: 2998
  year: 2021
  ident: R18
  article-title: Overcoming PD-1 blockade resistance with Cpg-A toll-like receptor 9 agonist vidutolimod in patients with metastatic melanoma
  publication-title: Cancer Discov
  doi: 10.1158/2159-8290.CD-21-0425
– volume: 8
  start-page: 1250
  year: 2018
  ident: R19
  article-title: SD-101 in combination with pembrolizumab in advanced melanoma: results of a phase IB, multicenter study
  publication-title: Cancer Discov
  doi: 10.1158/2159-8290.CD-18-0280
– volume: 83
  start-page: 1858
  year: 2023
  ident: R21
  article-title: Abstract 1858: enhanced delivery of anti PD-1 antibody to liver tumors in oncopig using pressure enabled drug delivery (PEDD) versus a systemic delivery
  publication-title: Cancer Res
  doi: 10.1158/1538-7445.AM2023-1858
– volume: 39
  start-page: 599
  year: 2021
  ident: R26
  article-title: Nivolumab and Ipilimumab in metastatic uveal melanoma: results from a single-arm phase II study
  publication-title: J Clin Oncol
  doi: 10.1200/JCO.20.00605
– volume: 14
  start-page: 3625
  year: 2020
  ident: R5
  article-title: Research status and outlook of PD-1/PD-L1 inhibitors for cancer therapy
  publication-title: Drug Des Devel Ther
  doi: 10.2147/DDDT.S267433
– volume: 125
  start-page: 3384
  year: 2015
  ident: R41
  article-title: Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future
  publication-title: J Clin Invest
  doi: 10.1172/JCI80011
– volume: 29
  start-page: 791
  year: 2018
  ident: R29
  article-title: Potential cost savings owing to the route of administration of oncology drugs: a microcosting study of intravenous and subcutaneous administration of trastuzumab and rituximab in the Netherlands
  publication-title: Anticancer Drugs
  doi: 10.1097/CAD.0000000000000648
– volume: 2
  year: 2017
  ident: R13
  article-title: Partially exhausted tumor-infiltrating lymphocytes predict response to combination immunotherapy
  publication-title: JCI Insight
  doi: 10.1172/jci.insight.93433
– volume: 8
  year: 2016
  ident: R4
  article-title: PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: mechanisms, response biomarkers, and combinations
  publication-title: Sci Transl Med
  doi: 10.1126/scitranslmed.aad7118
– volume: 29
  start-page: 1854
  year: 2022
  ident: R24
  article-title: Regional infusion of a class C Tlr9 agonist enhances liver tumor microenvironment reprogramming and MDSC reduction to improve responsiveness to systemic checkpoint inhibition
  publication-title: Cancer Gene Ther
  doi: 10.1038/s41417-022-00484-z
– volume: 22
  start-page: 793
  year: 2019
  ident: R9
  article-title: Predictive factors for hyperprogressive disease during Nivolumab as anti-Pd1 treatment in patients with advanced gastric cancer
  publication-title: Gastric Cancer
  doi: 10.1007/s10120-018-00922-8
– volume: 170
  start-page: 4061
  year: 2003
  ident: R39
  article-title: Cpg-A-induced monocyte IFN-gamma-inducible Protein-10 production is regulated by plasmacytoid dendritic cell-derived IFN-alpha
  publication-title: J Immunol
  doi: 10.4049/jimmunol.170.8.4061
– volume: 12
  year: 2021
  ident: R23
  article-title: Macrophage biology and mechanisms of immune suppression in breast cancer
  publication-title: Front Immunol
  doi: 10.3389/fimmu.2021.643771
– volume: 38
  start-page: 533
  year: 2019
  ident: R43
  article-title: Stat3 inhibition induces bax-dependent apoptosis in liver tumor myeloid-derived Suppressor cells
  publication-title: Oncogene
  doi: 10.1038/s41388-018-0449-z
– volume: 21
  start-page: 509
  year: 2022
  ident: R8
  article-title: The foundations of immune checkpoint blockade and the Ipilimumab approval decennial
  publication-title: Nat Rev Drug Discov
  doi: 10.1038/s41573-021-00345-8
– volume: 174
  start-page: 666
  year: 2023
  ident: R22
  article-title: Pressure-enabled drug delivery (PEDD) of a class C Tlr9 agonist in combination with checkpoint inhibitor therapy in a murine pancreatic cancer model
  publication-title: Surgery
  doi: 10.1016/j.surg.2023.05.011
– volume: 11
  year: 2020
  ident: R15
  article-title: Targeting myeloid-derived suppressor cell, a promising strategy to overcome resistance to immune checkpoint inhibitors
  publication-title: Front Immunol
  doi: 10.3389/fimmu.2020.00783
– volume: 126
  start-page: 3447
  year: 2016
  ident: R12
  article-title: Tumor immune profiling predicts response to anti-PD-1 therapy in human Melanoma
  publication-title: J Clin Invest
  doi: 10.1172/JCI87324
– volume: 192
  start-page: 1027
  year: 2000
  ident: R3
  article-title: Engagement of the PD-1 Immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation
  publication-title: J Exp Med
  doi: 10.1084/jem.192.7.1027
– volume: 5
  start-page: 1365
  year: 1999
  ident: R2
  article-title: B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and Interleukin-10 secretion
  publication-title: Nat Med
  doi: 10.1038/70932
– volume: 361
  start-page: 104295
  year: 2021
  ident: R45
  article-title: Mdscs in liver cancer: a critical tumor-promoting player and a potential therapeutic target
  publication-title: Cell Immunol
  doi: 10.1016/j.cellimm.2021.104295
– volume: 6
  start-page: 362
  year: 2021
  ident: R48
  article-title: Myeloid-derived suppressor cells as immunosuppressive regulators and therapeutic targets in cancer
  publication-title: Sig Transduct Target Ther
  doi: 10.1038/s41392-021-00670-9
– volume: 9
  year: 2021
  ident: R49
  article-title: Regional delivery of anti-PD-1 agent for colorectal liver metastases improves therapeutic index and anti-tumor activity
  publication-title: Vaccines (Basel)
  doi: 10.3390/vaccines9080807
– volume: 8
  year: 2020
  ident: R20
  article-title: HITM-SURE: hepatic immunotherapy for metastases phase IB anti-CEA CAR-T study utilizing pressure enabled drug delivery
  publication-title: J Immunother Cancer
  doi: 10.1136/jitc-2020-001097
– volume: 40
  start-page: 1021
  year: 2022
  ident: R32
  article-title: Phase I study of envafolimab (Kn035), a novel subcutaneous single-domain anti-PD-L1 monoclonal antibody, in Japanese patients with advanced solid tumors
  publication-title: Invest New Drugs
  doi: 10.1007/s10637-022-01287-7
– volume: 5
  start-page: 1411
  year: 2019
  ident: R10
  article-title: Five-year survival and correlates among patients with advanced melanoma, renal cell carcinoma, or non-small cell lung cancer treated with Nivolumab
  publication-title: JAMA Oncol
  doi: 10.1001/jamaoncol.2019.2187
– volume: 115
  start-page: 488
  year: 2024
  ident: R33
  article-title: Model-based dose selection of subcutaneous nivolumab in patients with advanced solid tumors
  publication-title: Clin Pharmacol Ther
  doi: 10.1002/cpt.3148
– volume: 113
  start-page: E7240
  year: 2016
  ident: R38
  article-title: Intratumoral injection of a Cpg oligonucleotide reverts resistance to PD-1 blockade by expanding multifunctional Cd8+ T cells
  publication-title: Proc Natl Acad Sci U S A
  doi: 10.1073/pnas.1608555113
– volume: 34
  start-page: 2210
  year: 2017
  ident: R34
  article-title: Subcutaneous Rituximab for the treatment of B-cell hematologic malignancies: a review of the scientific rationale and clinical development
  publication-title: Adv Ther
  doi: 10.1007/s12325-017-0610-z
– volume: 5
  start-page: 417
  year: 2017
  ident: R11
  article-title: Liver metastasis and treatment outcome with anti-PD-1 monoclonal antibody in patients with melanoma and NSCLC
  publication-title: Cancer Immunol Res
  doi: 10.1158/2326-6066.CIR-16-0325
– volume: 11
  year: 2016
  ident: R35
  article-title: Time savings with rituximab subcutaneous injection versus rituximab intravenous infusion: a time and motion study in eight countries
  publication-title: PLoS One
  doi: 10.1371/journal.pone.0157957
– volume: 328
  start-page: 267
  year: 1987
  ident: R1
  article-title: A new member of the immunoglobulin superfamily--CTLA-4
  publication-title: Nature New Biol
  doi: 10.1038/328267a0
– volume: 5
  start-page: 389
  year: 2016
  ident: R36
  article-title: A time and motion study of subcutaneous versus intravenous trastuzumab in patients with Her2-positive early breast cancer
  publication-title: Cancer Med
  doi: 10.1002/cam4.573
– volume: 39
  start-page: 586
  year: 2021
  ident: R27
  article-title: Nivolumab plus Ipilimumab for treatment-naive metastatic uveal melanoma: an open-label, multicenter, phase II trial by the Spanish multidisciplinary melanoma group (GEM-1402)
  publication-title: J Clin Oncol
  doi: 10.1200/JCO.20.00550
– volume: 63
  start-page: 247
  year: 2014
  ident: R16
  article-title: Frequencies of circulating MDSC correlate with clinical outcome of melanoma patients treated with Ipilimumab
  publication-title: Cancer Immunol Immunother
  doi: 10.1007/s00262-013-1508-5
– volume: 43
  start-page: 289
  year: 2023
  ident: R28
  article-title: Spending, utilization, and price trends for immune checkpoint inhibitors in US medicaid programs: an empirical analysis from 2011 to 2021
  publication-title: Clin Drug Investig
  doi: 10.1007/s40261-023-01254-x
– volume: 40
  start-page: 111295
  year: 2022
  ident: R47
  article-title: Tumor-infiltrated activated B cells suppress liver metastasis of colorectal cancers
  publication-title: Cell Rep
  doi: 10.1016/j.celrep.2022.111295
– volume: 5
  start-page: 999
  year: 2019
  ident: R30
  article-title: Assessment of subcutaneous vs intravenous administration of anti-PD-1 antibody PF-06801591 in patients with advanced solid tumors: a phase 1 dose-escalation trial
  publication-title: JAMA Oncol
  doi: 10.1001/jamaoncol.2019.0836
– volume: 16
  start-page: 563
  year: 2019
  ident: R50
  article-title: Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance
  publication-title: Nat Rev Clin Oncol
  doi: 10.1038/s41571-019-0218-0
– volume: 26
  start-page: e1514
  year: 2021
  ident: R31
  article-title: First-in-human phase I study of envafolimab, a novel subcutaneous single-domain anti-PD-L1 antibody, in patients with advanced solid tumors
  publication-title: Oncologist
  doi: 10.1002/onco.13817
– volume: 83
  start-page: 731
  year: 2023
  ident: R6
  article-title: Retifanlimab: first approval
  publication-title: Drugs (Abingdon Engl)
  doi: 10.1007/s40265-023-01884-7
– volume: 200
  start-page: 422
  year: 2018
  ident: R14
  article-title: Myeloid-derived Suppressor cells: immune-suppressive cells that impair antitumor immunity and are sculpted by their environment
  publication-title: J Immunol
  doi: 10.4049/jimmunol.1701019
– volume: 27
  start-page: 152
  year: 2021
  ident: R17
  article-title: Liver metastasis restrains immunotherapy efficacy via macrophage-mediated T cell elimination
  publication-title: Nat Med
  doi: 10.1038/s41591-020-1131-x
– volume: 388
  start-page: 2145
  year: 2023
  ident: R7
  article-title: Dostarlimab for primary advanced or recurrent endometrial cancer
  publication-title: N Engl J Med
  doi: 10.1056/NEJMoa2216334
– volume: 96
  start-page: 883
  year: 2014
  ident: R46
  article-title: Liver metastases induce reversible hepatic B cell dysfunction mediated by Gr-1+Cd11B+ myeloid cells
  publication-title: J Leukoc Biol
  doi: 10.1189/jlb.3A0114-012RR
– ident: 2025100304432731000_12.7.e008837.2
  doi: 10.1038/70932
– ident: 2025100304432731000_12.7.e008837.17
  doi: 10.1038/s41591-020-1131-x
– volume: 14
  start-page: 3625
  year: 2020
  ident: 2025100304432731000_12.7.e008837.5
  article-title: Research status and outlook of PD-1/PD-L1 inhibitors for cancer therapy
  publication-title: Drug Des Devel Ther
  doi: 10.2147/DDDT.S267433
– volume: 115
  start-page: 488
  year: 2024
  ident: 2025100304432731000_12.7.e008837.33
  article-title: Model-based dose selection of subcutaneous nivolumab in patients with advanced solid tumors
  publication-title: Clin Pharmacol Ther
  doi: 10.1002/cpt.3148
– volume: 38
  start-page: 533
  year: 2019
  ident: 2025100304432731000_12.7.e008837.43
  article-title: Stat3 inhibition induces bax-dependent apoptosis in liver tumor myeloid-derived Suppressor cells
  publication-title: Oncogene
  doi: 10.1038/s41388-018-0449-z
– ident: 2025100304432731000_12.7.e008837.16
  doi: 10.1007/s00262-013-1508-5
– ident: 2025100304432731000_12.7.e008837.3
  doi: 10.1084/jem.192.7.1027
– ident: 2025100304432731000_12.7.e008837.14
  doi: 10.4049/jimmunol.1701019
– ident: 2025100304432731000_12.7.e008837.46
  doi: 10.1189/jlb.3A0114-012RR
– volume: 8
  year: 2016
  ident: 2025100304432731000_12.7.e008837.4
  article-title: PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: mechanisms, response biomarkers, and combinations
  publication-title: Sci Transl Med
  doi: 10.1126/scitranslmed.aad7118
– volume: 40
  start-page: 1021
  year: 2022
  ident: 2025100304432731000_12.7.e008837.32
  article-title: Phase I study of envafolimab (Kn035), a novel subcutaneous single-domain anti-PD-L1 monoclonal antibody, in Japanese patients with advanced solid tumors
  publication-title: Invest New Drugs
  doi: 10.1007/s10637-022-01287-7
– ident: 2025100304432731000_12.7.e008837.37
  doi: 10.1093/annonc/mdw685
– volume: 26
  start-page: e1514
  year: 2021
  ident: 2025100304432731000_12.7.e008837.31
  article-title: First-in-human phase I study of envafolimab, a novel subcutaneous single-domain anti-PD-L1 antibody, in patients with advanced solid tumors
  publication-title: Oncologist
  doi: 10.1002/onco.13817
– volume: 5
  start-page: 389
  year: 2016
  ident: 2025100304432731000_12.7.e008837.36
  article-title: A time and motion study of subcutaneous versus intravenous trastuzumab in patients with Her2-positive early breast cancer
  publication-title: Cancer Med
  doi: 10.1002/cam4.573
– volume: 328
  start-page: 267
  year: 1987
  ident: 2025100304432731000_12.7.e008837.1
  article-title: A new member of the immunoglobulin superfamily--CTLA-4
  publication-title: Nature New Biol
  doi: 10.1038/328267a0
– ident: 2025100304432731000_12.7.e008837.12
  doi: 10.1172/JCI87324
– volume: 34
  start-page: 2210
  year: 2017
  ident: 2025100304432731000_12.7.e008837.34
  article-title: Subcutaneous Rituximab for the treatment of B-cell hematologic malignancies: a review of the scientific rationale and clinical development
  publication-title: Adv Ther
  doi: 10.1007/s12325-017-0610-z
– volume: 174
  start-page: 666
  year: 2023
  ident: 2025100304432731000_12.7.e008837.22
  article-title: Pressure-enabled drug delivery (PEDD) of a class C Tlr9 agonist in combination with checkpoint inhibitor therapy in a murine pancreatic cancer model
  publication-title: Surgery
  doi: 10.1016/j.surg.2023.05.011
– ident: 2025100304432731000_12.7.e008837.39
  doi: 10.4049/jimmunol.170.8.4061
– volume: 11
  year: 2016
  ident: 2025100304432731000_12.7.e008837.35
  article-title: Time savings with rituximab subcutaneous injection versus rituximab intravenous infusion: a time and motion study in eight countries
  publication-title: PLoS One
  doi: 10.1371/journal.pone.0157957
– volume: 83
  start-page: 731
  year: 2023
  ident: 2025100304432731000_12.7.e008837.6
  article-title: Retifanlimab: first approval
  publication-title: Drugs (Abingdon Engl)
– volume: 5
  start-page: 999
  year: 2019
  ident: 2025100304432731000_12.7.e008837.30
  article-title: Assessment of subcutaneous vs intravenous administration of anti-PD-1 antibody PF-06801591 in patients with advanced solid tumors: a phase 1 dose-escalation trial
  publication-title: JAMA Oncol
  doi: 10.1001/jamaoncol.2019.0836
– ident: 2025100304432731000_12.7.e008837.26
  doi: 10.1200/JCO.20.00605
– volume: 5
  start-page: 1411
  year: 2019
  ident: 2025100304432731000_12.7.e008837.10
  article-title: Five-year survival and correlates among patients with advanced melanoma, renal cell carcinoma, or non-small cell lung cancer treated with Nivolumab
  publication-title: JAMA Oncol
  doi: 10.1001/jamaoncol.2019.2187
– volume: 8
  year: 2020
  ident: 2025100304432731000_12.7.e008837.20
  article-title: HITM-SURE: hepatic immunotherapy for metastases phase IB anti-CEA CAR-T study utilizing pressure enabled drug delivery
  publication-title: J Immunother Cancer
  doi: 10.1136/jitc-2020-001097
– ident: 2025100304432731000_12.7.e008837.27
  doi: 10.1200/jco.20.00550
– volume: 6
  start-page: 362
  year: 2021
  ident: 2025100304432731000_12.7.e008837.48
  article-title: Myeloid-derived suppressor cells as immunosuppressive regulators and therapeutic targets in cancer
  publication-title: Sig Transduct Target Ther
  doi: 10.1038/s41392-021-00670-9
– volume: 2
  year: 2017
  ident: 2025100304432731000_12.7.e008837.13
  article-title: Partially exhausted tumor-infiltrating lymphocytes predict response to combination immunotherapy
  publication-title: JCI Insight
  doi: 10.1172/jci.insight.93433
– ident: 2025100304432731000_12.7.e008837.44
– volume: 40
  start-page: 111295
  year: 2022
  ident: 2025100304432731000_12.7.e008837.47
  article-title: Tumor-infiltrated activated B cells suppress liver metastasis of colorectal cancers
  publication-title: Cell Rep
  doi: 10.1016/j.celrep.2022.111295
– ident: 2025100304432731000_12.7.e008837.40
– ident: 2025100304432731000_12.7.e008837.50
  doi: 10.1038/s41571-019-0218-0
– volume: 9
  year: 2021
  ident: 2025100304432731000_12.7.e008837.49
  article-title: Regional delivery of anti-PD-1 agent for colorectal liver metastases improves therapeutic index and anti-tumor activity
  publication-title: Vaccines (Basel)
  doi: 10.3390/vaccines9080807
– volume: 12
  year: 2021
  ident: 2025100304432731000_12.7.e008837.23
  article-title: Macrophage biology and mechanisms of immune suppression in breast cancer
  publication-title: Front Immunol
  doi: 10.3389/fimmu.2021.643771
– ident: 2025100304432731000_12.7.e008837.11
  doi: 10.1158/2326-6066.CIR-16-0325
– volume: 11
  year: 2020
  ident: 2025100304432731000_12.7.e008837.15
  article-title: Targeting myeloid-derived suppressor cell, a promising strategy to overcome resistance to immune checkpoint inhibitors
  publication-title: Front Immunol
  doi: 10.3389/fimmu.2020.00783
– volume: 29
  start-page: 791
  year: 2018
  ident: 2025100304432731000_12.7.e008837.29
  article-title: Potential cost savings owing to the route of administration of oncology drugs: a microcosting study of intravenous and subcutaneous administration of trastuzumab and rituximab in the Netherlands
  publication-title: Anticancer Drugs
  doi: 10.1097/CAD.0000000000000648
– ident: 2025100304432731000_12.7.e008837.19
  doi: 10.1158/2159-8290.CD-18-0280
– volume: 83
  start-page: 1858
  year: 2023
  ident: 2025100304432731000_12.7.e008837.21
  article-title: Abstract 1858: enhanced delivery of anti PD-1 antibody to liver tumors in oncopig using pressure enabled drug delivery (PEDD) versus a systemic delivery
  publication-title: Cancer Res
  doi: 10.1158/1538-7445.AM2023-1858
– volume: 43
  start-page: 289
  year: 2023
  ident: 2025100304432731000_12.7.e008837.28
  article-title: Spending, utilization, and price trends for immune checkpoint inhibitors in US medicaid programs: an empirical analysis from 2011 to 2021
  publication-title: Clin Drug Investig
  doi: 10.1007/s40261-023-01254-x
– ident: 2025100304432731000_12.7.e008837.38
  doi: 10.1073/pnas.1608555113
– volume: 21
  start-page: 509
  year: 2022
  ident: 2025100304432731000_12.7.e008837.8
  article-title: The foundations of immune checkpoint blockade and the Ipilimumab approval decennial
  publication-title: Nat Rev Drug Discov
  doi: 10.1038/s41573-021-00345-8
– ident: 2025100304432731000_12.7.e008837.42
  doi: 10.1136/jitc-2022-SITC2022.1165
– ident: 2025100304432731000_12.7.e008837.18
  doi: 10.1158/2159-8290.CD-21-0425
– ident: #cr-split#-2025100304432731000_12.7.e008837.25.1
  doi: 10.1136/jitc-2023-SITC2023.1534
– ident: 2025100304432731000_12.7.e008837.41
  doi: 10.1172/JCI80011
– volume: 361
  start-page: 104295
  year: 2021
  ident: 2025100304432731000_12.7.e008837.45
  article-title: Mdscs in liver cancer: a critical tumor-promoting player and a potential therapeutic target
  publication-title: Cell Immunol
  doi: 10.1016/j.cellimm.2021.104295
– volume: 29
  start-page: 1854
  year: 2022
  ident: 2025100304432731000_12.7.e008837.24
  article-title: Regional infusion of a class C Tlr9 agonist enhances liver tumor microenvironment reprogramming and MDSC reduction to improve responsiveness to systemic checkpoint inhibition
  publication-title: Cancer Gene Ther
  doi: 10.1038/s41417-022-00484-z
– ident: #cr-split#-2025100304432731000_12.7.e008837.25.2
  doi: 10.1136/jitc-2023-SITC2023.1534
– volume: 388
  start-page: 2145
  year: 2023
  ident: 2025100304432731000_12.7.e008837.7
  article-title: Dostarlimab for primary advanced or recurrent endometrial cancer
  publication-title: N Engl J Med
  doi: 10.1056/NEJMoa2216334
– volume: 22
  start-page: 793
  year: 2019
  ident: 2025100304432731000_12.7.e008837.9
  article-title: Predictive factors for hyperprogressive disease during Nivolumab as anti-Pd1 treatment in patients with advanced gastric cancer
  publication-title: Gastric Cancer
  doi: 10.1007/s10120-018-00922-8
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Snippet BackgroundToll-like receptor 9 (TLR9) agonists induce inflammatory responses that promote the killing of infectious micro-organisms, cancer cells and develop...
Toll-like receptor 9 (TLR9) agonists induce inflammatory responses that promote the killing of infectious micro-organisms, cancer cells and develop adaptive...
Background Toll-like receptor 9 (TLR9) agonists induce inflammatory responses that promote the killing of infectious micro-organisms, cancer cells and develop...
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StartPage e008837
SubjectTerms Animals
Antigen presentation
Bioluminescence
Cell Line, Tumor
Clinical/Translational Cancer Immunotherapy
Costs
Drug Delivery Systems
Drug dosages
Humans
Immune Checkpoint Inhibitor
Immune checkpoint inhibitors
Immune Checkpoint Inhibitors - administration & dosage
Immune Checkpoint Inhibitors - pharmacology
Immune Checkpoint Inhibitors - therapeutic use
Inflammation
Liver
Liver cancer
Liver Neoplasms - drug therapy
Liver Neoplasms - secondary
Melanoma
Metastasis
Mice
Mice, Inbred C57BL
Myeloid-derived suppressor cell - MDSC
Myeloid-Derived Suppressor Cells - drug effects
Myeloid-Derived Suppressor Cells - immunology
Myeloid-Derived Suppressor Cells - metabolism
Original Research
Patient satisfaction
Toll-like receptor - TLR
Tumor microenvironment - TME
Tumors
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Title Subcutaneous checkpoint inhibition is equivalent to systemic delivery when combined with nelitolimod delivered via pressure-enabled drug delivery for depletion of intrahepatic myeloid-derived suppressor cells and control of liver metastases
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