Neoadjuvant immune checkpoint blockade triggers persistent and systemic T reg activation which blunts therapeutic efficacy against metastatic spread of breast tumors

The clinical successes of immune checkpoint blockade (ICB) in advanced cancer patients have recently spurred the clinical implementation of ICB in the neoadjuvant and perioperative setting. However, how neoadjuvant ICB therapy affects the systemic immune landscape and metastatic spread remains to be...

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Published in:	Oncoimmunology Vol. 12; no. 1; p. 2201147
Main Authors:	Blomberg, Olga S., Kos, Kevin, Spagnuolo, Lorenzo, Isaeva, Olga I., Garner, Hannah, Wellenstein, Max D., Bakker, Noor, Duits, Danique E.M., Kersten, Kelly, Klarenbeek, Sjoerd, Hau, Cheei-Sing, Kaldenbach, Daphne, Raeven, Elisabeth A.M., Vrijland, Kim, Kok, Marleen, de Visser, Karin E.
Format:	Journal Article
Language:	English
Published:	United States 31.12.2023
Subjects:	Animals Breast Neoplasms - immunology Breast Neoplasms - therapy CD8-Positive T-Lymphocytes - immunology Humans Immune Checkpoint Inhibitors - therapeutic use Killer Cells, Natural - immunology Lymphocyte Activation Mice Myeloid Cells - immunology Neoadjuvant Therapy Neoplasm Metastasis T-Lymphocytes, Regulatory - immunology regulatory T cells Breast cancer metastasis myeloid cells resistance mechanisms neoadjuvant immune checkpoint blockade
ISSN:	2162-402X, 2162-402X
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Abstract	The clinical successes of immune checkpoint blockade (ICB) in advanced cancer patients have recently spurred the clinical implementation of ICB in the neoadjuvant and perioperative setting. However, how neoadjuvant ICB therapy affects the systemic immune landscape and metastatic spread remains to be established. Tumors promote both local and systemic expansion of regulatory T cells (T ), which are key orchestrators of tumor-induced immunosuppression, contributing to immune evasion, tumor progression and metastasis. T express inhibitory immune checkpoint molecules and thus may be unintended targets for ICB therapy counteracting its efficacy. Using ICB-refractory models of spontaneous primary and metastatic breast cancer that recapitulate the poor ICB response of breast cancer patients, we observed that combined anti-PD-1 and anti-CTLA-4 therapy inadvertently promotes proliferation and activation of T in the tumor, tumor-draining lymph node and circulation. Also in breast cancer patients, T levels were elevated upon ICB. Depletion of T during neoadjuvant ICB in tumor-bearing mice not only reshaped the intratumoral immune landscape into a state favorable for ICB response but also induced profound and persistent alterations in systemic immunity, characterized by elevated CD8+ T cells and NK cells and durable T cell activation that was maintained after treatment cessation. While depletion of T in combination with neoadjuvant ICB did not inhibit primary tumor growth, it prolonged metastasis-related survival driven predominantly by CD8+ T cells. This study demonstrates that neoadjuvant ICB therapy of breast cancer can be empowered by simultaneous targeting of T extending metastasis-related survival, independent of a primary tumor response.
AbstractList	The clinical successes of immune checkpoint blockade (ICB) in advanced cancer patients have recently spurred the clinical implementation of ICB in the neoadjuvant and perioperative setting. However, how neoadjuvant ICB therapy affects the systemic immune landscape and metastatic spread remains to be established. Tumors promote both local and systemic expansion of regulatory T cells (T ), which are key orchestrators of tumor-induced immunosuppression, contributing to immune evasion, tumor progression and metastasis. T express inhibitory immune checkpoint molecules and thus may be unintended targets for ICB therapy counteracting its efficacy. Using ICB-refractory models of spontaneous primary and metastatic breast cancer that recapitulate the poor ICB response of breast cancer patients, we observed that combined anti-PD-1 and anti-CTLA-4 therapy inadvertently promotes proliferation and activation of T in the tumor, tumor-draining lymph node and circulation. Also in breast cancer patients, T levels were elevated upon ICB. Depletion of T during neoadjuvant ICB in tumor-bearing mice not only reshaped the intratumoral immune landscape into a state favorable for ICB response but also induced profound and persistent alterations in systemic immunity, characterized by elevated CD8+ T cells and NK cells and durable T cell activation that was maintained after treatment cessation. While depletion of T in combination with neoadjuvant ICB did not inhibit primary tumor growth, it prolonged metastasis-related survival driven predominantly by CD8+ T cells. This study demonstrates that neoadjuvant ICB therapy of breast cancer can be empowered by simultaneous targeting of T extending metastasis-related survival, independent of a primary tumor response.
Author	Kersten, Kelly Spagnuolo, Lorenzo Isaeva, Olga I. Vrijland, Kim Hau, Cheei-Sing Kaldenbach, Daphne Garner, Hannah Kos, Kevin Kok, Marleen Raeven, Elisabeth A.M. Blomberg, Olga S. Klarenbeek, Sjoerd Duits, Danique E.M. Wellenstein, Max D. de Visser, Karin E. Bakker, Noor
Author_xml	– sequence: 1 givenname: Olga S. surname: Blomberg fullname: Blomberg, Olga S. organization: Division of Tumor Biology & Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands, Oncode Institute, Utrecht, The Netherlands, Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands – sequence: 2 givenname: Kevin surname: Kos fullname: Kos, Kevin organization: Division of Tumor Biology & Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands, Oncode Institute, Utrecht, The Netherlands, Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands – sequence: 3 givenname: Lorenzo surname: Spagnuolo fullname: Spagnuolo, Lorenzo organization: Division of Tumor Biology & Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands, Oncode Institute, Utrecht, The Netherlands – sequence: 4 givenname: Olga I. surname: Isaeva fullname: Isaeva, Olga I. organization: Division of Tumor Biology & Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands – sequence: 5 givenname: Hannah surname: Garner fullname: Garner, Hannah organization: Division of Tumor Biology & Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands, Oncode Institute, Utrecht, The Netherlands – sequence: 6 givenname: Max D. surname: Wellenstein fullname: Wellenstein, Max D. organization: Division of Tumor Biology & Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands, Oncode Institute, Utrecht, The Netherlands, Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands – sequence: 7 givenname: Noor surname: Bakker fullname: Bakker, Noor organization: Division of Tumor Biology & Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands, Oncode Institute, Utrecht, The Netherlands, Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands – sequence: 8 givenname: Danique E.M. surname: Duits fullname: Duits, Danique E.M. organization: Division of Tumor Biology & Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands, Oncode Institute, Utrecht, The Netherlands, Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands – sequence: 9 givenname: Kelly surname: Kersten fullname: Kersten, Kelly organization: Division of Tumor Biology & Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands – sequence: 10 givenname: Sjoerd surname: Klarenbeek fullname: Klarenbeek, Sjoerd organization: Experimental Animal Pathology Facility, Netherlands Cancer Institute, Amsterdam, Netherlands – sequence: 11 givenname: Cheei-Sing surname: Hau fullname: Hau, Cheei-Sing organization: Division of Tumor Biology & Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands, Oncode Institute, Utrecht, The Netherlands – sequence: 12 givenname: Daphne surname: Kaldenbach fullname: Kaldenbach, Daphne organization: Division of Tumor Biology & Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands, Oncode Institute, Utrecht, The Netherlands – sequence: 13 givenname: Elisabeth A.M. surname: Raeven fullname: Raeven, Elisabeth A.M. organization: Division of Tumor Biology & Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands, Oncode Institute, Utrecht, The Netherlands – sequence: 14 givenname: Kim surname: Vrijland fullname: Vrijland, Kim organization: Division of Tumor Biology & Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands, Oncode Institute, Utrecht, The Netherlands – sequence: 15 givenname: Marleen surname: Kok fullname: Kok, Marleen organization: Division of Tumor Biology & Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands, Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands – sequence: 16 givenname: Karin E. orcidid: 0000-0002-0293-868X surname: de Visser fullname: de Visser, Karin E. organization: Division of Tumor Biology & Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands, Oncode Institute, Utrecht, The Netherlands, Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands
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Cites_doi	10.1101/gad.279190.116 10.1016/j.ccell.2022.01.001 10.1186/s13058-014-0432-8 10.1038/ni1428 10.1186/s12885-015-1742-7 10.1371/journal.pone.0008437 10.1016/j.ccell.2022.11.014 10.1038/ni.3004 10.1155/2021/6658324 10.1158/0008-5472.CAN-16-0194 10.1038/cti.2016.16 10.1038/ni.3159 10.1158/0008-5472.CAN-11-4208 10.1073/pnas.2114282119 10.1038/s43018-022-00447-1 10.1038/nri3862 10.1016/j.celrep.2020.108482 10.1016/s0140-6736(20)32531-9 10.1172/jci90499 10.1016/j.immuni.2013.07.012 10.1038/s41577-019-0271-z 10.1038/nature14282 10.1016/bs.mie.2019.07.035 10.1007/s00432-012-1258-3 10.1016/j.ejca.2021.04.035 10.1172/JCI73639 10.1084/jem.20212169 10.1038/s41556-019-0298-1 10.1016/j.ccr.2006.09.013 10.1038/s41591-019-0432-4 10.1109/MCSE.2007.55 10.1038/s41556-019-0373-7 10.1016/j.immuni.2016.10.032 10.1186/s40425-019-0768-9 10.1097/ACI.0b013e328334f693 10.1016/j.cell.2021.05.027 10.1093/annonc/mdy518 10.1038/s41467-020-17046-2 10.1038/s43018-020-00133-0 10.1038/s41586-019-1450-6 10.1073/pnas.1822001116 10.1172/jci.insight.124507 10.1158/1078-0432.ccr-06-2347 10.1002/ijc.32829 10.1038/s43018-023-00542-x 10.1038/s41591-018-0198-0 10.25080/Majora-92bf1922-00a 10.3389/fimmu.2020.583084 10.1016/S0140-6736(20)31953-X 10.1182/blood-2007-11-125435 10.1136/jitc-2020-001749 10.1038/s41423-018-0004-4 10.1038/s41590-019-0429-7 10.1038/s41590-020-0769-3 10.1038/s41591-019-0357-y 10.1038/s41598-022-07153-z 10.1038/s41467-019-11911-5 10.1038/s41591-020-0805-8 10.1146/annurev-cancerbio-042920-104912 10.1038/nm.3909 10.1056/NEJMoa2112651 10.1158/1078-0432.CCR-18-0762 10.1158/1078-0432.CCR-19-1868 10.1016/j.cell.2016.12.022 10.21105/joss.03021 10.1016/j.celrep.2022.110447 10.1084/jem.20130762 10.1186/s40425-019-0605-1 10.1038/s41523-022-00386-1 10.1016/j.cell.2019.02.005 10.1146/annurev-cancerbio-030419-033428 10.1097/CJI.0b013e3181fad2b0 10.1038/s41416-022-01743-4 10.1080/2162402X.2020.1727116 10.1038/s41590-019-0321-5 10.1186/s12885-021-08636-4 10.1016/j.annonc.2022.07.1940
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Keywords	regulatory T cells Breast cancer metastasis myeloid cells resistance mechanisms neoadjuvant immune checkpoint blockade
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References	e_1_3_6_30_1 e_1_3_6_53_1 e_1_3_6_76_1 e_1_3_6_32_1 e_1_3_6_55_1 e_1_3_6_74_1 e_1_3_6_11_1 e_1_3_6_72_1 e_1_3_6_51_1 e_1_3_6_70_1 e_1_3_6_15_1 e_1_3_6_38_1 e_1_3_6_13_1 e_1_3_6_19_1 e_1_3_6_34_1 e_1_3_6_57_1 e_1_3_6_17_1 e_1_3_6_36_1 e_1_3_6_59_1 e_1_3_6_78_1 e_1_3_6_42_1 e_1_3_6_65_1 e_1_3_6_21_1 e_1_3_6_44_1 e_1_3_6_63_1 e_1_3_6_2_1 e_1_3_6_61_1 e_1_3_6_40_1 e_1_3_6_6_1 e_1_3_6_80_1 e_1_3_6_4_1 e_1_3_6_8_1 e_1_3_6_27_1 e_1_3_6_29_1 e_1_3_6_23_1 e_1_3_6_46_1 e_1_3_6_69_1 e_1_3_6_25_1 e_1_3_6_48_1 e_1_3_6_67_1 e_1_3_6_31_1 e_1_3_6_52_1 e_1_3_6_77_1 e_1_3_6_33_1 e_1_3_6_54_1 e_1_3_6_75_1 e_1_3_6_10_1 e_1_3_6_73_1 e_1_3_6_50_1 e_1_3_6_71_1 e_1_3_6_14_1 e_1_3_6_39_1 e_1_3_6_12_1 e_1_3_6_18_1 e_1_3_6_35_1 e_1_3_6_56_1 e_1_3_6_16_1 e_1_3_6_37_1 e_1_3_6_58_1 e_1_3_6_79_1 e_1_3_6_20_1 e_1_3_6_41_1 e_1_3_6_66_1 e_1_3_6_22_1 e_1_3_6_43_1 e_1_3_6_64_1 e_1_3_6_62_1 e_1_3_6_81_1 e_1_3_6_60_1 e_1_3_6_5_1 e_1_3_6_3_1 e_1_3_6_9_1 e_1_3_6_7_1 e_1_3_6_28_1 e_1_3_6_49_1 e_1_3_6_24_1 e_1_3_6_45_1 e_1_3_6_26_1 e_1_3_6_47_1 e_1_3_6_68_1
References_xml	– ident: e_1_3_6_44_1 doi: 10.1101/gad.279190.116 – ident: e_1_3_6_29_1 doi: 10.1016/j.ccell.2022.01.001 – ident: e_1_3_6_17_1 doi: 10.1186/s13058-014-0432-8 – ident: e_1_3_6_46_1 doi: 10.1038/ni1428 – ident: e_1_3_6_23_1 doi: 10.1186/s12885-015-1742-7 – ident: e_1_3_6_48_1 doi: 10.1371/journal.pone.0008437 – ident: e_1_3_6_41_1 doi: 10.1016/j.ccell.2022.11.014 – ident: e_1_3_6_61_1 doi: 10.1038/ni.3004 – ident: e_1_3_6_47_1 doi: 10.1155/2021/6658324 – ident: e_1_3_6_62_1 doi: 10.1158/0008-5472.CAN-16-0194 – ident: e_1_3_6_28_1 doi: 10.1038/cti.2016.16 – ident: e_1_3_6_54_1 doi: 10.1038/ni.3159 – ident: e_1_3_6_40_1 doi: 10.1158/0008-5472.CAN-11-4208 – ident: e_1_3_6_74_1 doi: 10.1073/pnas.2114282119 – ident: e_1_3_6_72_1 doi: 10.1038/s43018-022-00447-1 – ident: e_1_3_6_50_1 doi: 10.1038/nri3862 – ident: e_1_3_6_19_1 doi: 10.1016/j.celrep.2020.108482 – ident: e_1_3_6_4_1 doi: 10.1016/s0140-6736(20)32531-9 – ident: e_1_3_6_35_1 doi: 10.1172/jci90499 – ident: e_1_3_6_27_1 doi: 10.1016/j.immuni.2013.07.012 – ident: e_1_3_6_13_1 doi: 10.1038/s41577-019-0271-z – ident: e_1_3_6_57_1 doi: 10.1038/nature14282 – ident: e_1_3_6_75_1 doi: 10.1016/bs.mie.2019.07.035 – ident: e_1_3_6_20_1 doi: 10.1007/s00432-012-1258-3 – ident: e_1_3_6_5_1 doi: 10.1016/j.ejca.2021.04.035 – ident: e_1_3_6_52_1 doi: 10.1172/JCI73639 – ident: e_1_3_6_49_1 doi: 10.1084/jem.20212169 – ident: e_1_3_6_67_1 doi: 10.1038/s41556-019-0298-1 – ident: e_1_3_6_39_1 doi: 10.1016/j.ccr.2006.09.013 – ident: e_1_3_6_3_1 doi: 10.1038/s41591-019-0432-4 – ident: e_1_3_6_80_1 doi: 10.1109/MCSE.2007.55 – ident: e_1_3_6_69_1 doi: 10.1038/s41556-019-0373-7 – ident: e_1_3_6_16_1 doi: 10.1016/j.immuni.2016.10.032 – ident: e_1_3_6_59_1 doi: 10.1186/s40425-019-0768-9 – ident: e_1_3_6_65_1 doi: 10.1097/ACI.0b013e328334f693 – ident: e_1_3_6_73_1 doi: 10.1016/j.cell.2021.05.027 – ident: e_1_3_6_2_1 doi: 10.1093/annonc/mdy518 – ident: e_1_3_6_24_1 doi: 10.1038/s41467-020-17046-2 – ident: e_1_3_6_36_1 doi: 10.1038/s43018-020-00133-0 – ident: e_1_3_6_43_1 doi: 10.1038/s41586-019-1450-6 – ident: e_1_3_6_34_1 doi: 10.1073/pnas.1822001116 – ident: e_1_3_6_12_1 doi: 10.1172/jci.insight.124507 – ident: e_1_3_6_77_1 – ident: e_1_3_6_21_1 doi: 10.1158/1078-0432.ccr-06-2347 – ident: e_1_3_6_55_1 doi: 10.1002/ijc.32829 – ident: e_1_3_6_45_1 doi: 10.1038/s43018-023-00542-x – ident: e_1_3_6_7_1 doi: 10.1038/s41591-018-0198-0 – ident: e_1_3_6_78_1 doi: 10.25080/Majora-92bf1922-00a – ident: e_1_3_6_60_1 doi: 10.3389/fimmu.2020.583084 – ident: e_1_3_6_9_1 doi: 10.1016/S0140-6736(20)31953-X – ident: e_1_3_6_31_1 doi: 10.1182/blood-2007-11-125435 – ident: e_1_3_6_38_1 doi: 10.1136/jitc-2020-001749 – ident: e_1_3_6_70_1 doi: 10.1038/s41423-018-0004-4 – ident: e_1_3_6_22_1 doi: 10.1038/s41590-019-0429-7 – ident: e_1_3_6_30_1 doi: 10.1038/s41590-020-0769-3 – ident: e_1_3_6_33_1 doi: 10.1038/s41591-019-0357-y – ident: e_1_3_6_37_1 doi: 10.1038/s41598-022-07153-z – ident: e_1_3_6_64_1 doi: 10.1038/s41467-019-11911-5 – ident: e_1_3_6_81_1 – ident: e_1_3_6_6_1 doi: 10.1038/s41591-020-0805-8 – ident: e_1_3_6_15_1 doi: 10.1146/annurev-cancerbio-042920-104912 – ident: e_1_3_6_68_1 doi: 10.1038/nm.3909 – ident: e_1_3_6_8_1 doi: 10.1056/NEJMoa2112651 – ident: e_1_3_6_32_1 doi: 10.1158/1078-0432.CCR-18-0762 – ident: e_1_3_6_66_1 doi: 10.1158/1078-0432.CCR-19-1868 – ident: e_1_3_6_76_1 – ident: e_1_3_6_11_1 doi: 10.1016/j.cell.2016.12.022 – ident: e_1_3_6_79_1 doi: 10.21105/joss.03021 – ident: e_1_3_6_26_1 doi: 10.1016/j.celrep.2022.110447 – ident: e_1_3_6_18_1 doi: 10.1084/jem.20130762 – ident: e_1_3_6_25_1 doi: 10.1186/s40425-019-0605-1 – ident: e_1_3_6_71_1 doi: 10.1038/s41523-022-00386-1 – ident: e_1_3_6_56_1 doi: 10.1016/j.cell.2019.02.005 – ident: e_1_3_6_14_1 doi: 10.1146/annurev-cancerbio-030419-033428 – ident: e_1_3_6_51_1 doi: 10.1097/CJI.0b013e3181fad2b0 – ident: e_1_3_6_58_1 doi: 10.1038/s41416-022-01743-4 – ident: e_1_3_6_53_1 doi: 10.1080/2162402X.2020.1727116 – ident: e_1_3_6_63_1 doi: 10.1038/s41590-019-0321-5 – ident: e_1_3_6_42_1 doi: 10.1186/s12885-021-08636-4 – ident: e_1_3_6_10_1 doi: 10.1016/j.annonc.2022.07.1940
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Snippet	The clinical successes of immune checkpoint blockade (ICB) in advanced cancer patients have recently spurred the clinical implementation of ICB in the...
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SubjectTerms	Animals Breast Neoplasms - immunology Breast Neoplasms - therapy CD8-Positive T-Lymphocytes - immunology Humans Immune Checkpoint Inhibitors - therapeutic use Killer Cells, Natural - immunology Lymphocyte Activation Mice Myeloid Cells - immunology Neoadjuvant Therapy Neoplasm Metastasis T-Lymphocytes, Regulatory - immunology
Title	Neoadjuvant immune checkpoint blockade triggers persistent and systemic T reg activation which blunts therapeutic efficacy against metastatic spread of breast tumors
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