Combination PD-1 and PD-L1 Blockade Promotes Durable Neoantigen-Specific T Cell-Mediated Immunity in Pancreatic Ductal Adenocarcinoma

Adam L. Burrack; Ellen J. Spartz; Jackson F. Raynor; Iris Wang; Margaret Olson; Ingunn M. Stromnes

doi:10.1016/j.celrep.2019.07.059

Combination PD-1 and PD-L1 Blockade Promotes Durable Neoantigen-Specific T Cell-Mediated Immunity in Pancreatic Ductal Adenocarcinoma

Adam L. Burrack, Ellen J. Spartz, Jackson F. Raynor, Iris Wang, Margaret Olson, Ingunn M. Stromnes

Microbiology

Research output: Contribution to journal › Article › peer-review

64 Scopus citations

Abstract

Burrack et al. investigate tumor-specific T cells during immunotherapy of pancreas cancer. T cells accumulate intratumorally yet rapidly exhaust. Combined PD-1 + PD-L1 blockade promotes peripheral T cell expansion, TNFα production, and eradication of spontaneous tumor recurrence in 50% of animals. Tumor variants defective in IFNγ-inducible Tap1 and MHC class I ultimately emerge.

Original language	English (US)
Pages (from-to)	2140-2155.e6
Journal	Cell reports
Volume	28
Issue number	8
DOIs	https://doi.org/10.1016/j.celrep.2019.07.059
State	Published - Aug 20 2019

Bibliographical note

Funding Information:
We thank Dr. Pamela Rosato for help generating the CB tetramer. We thank the NIH Tetramer Core for generously supplying us with fluorescently labeled Ova 257–264 :H-2K b tetramer. We thank Dr. Jason Mitchell at the Center for Immunology (CFI) for initial help with microscopy. We thank colleagues at the CFI at the University of Minnesota for helpful discussions. A.L.B. is supported by a computational training award from the American Association of Immunologists . E.J.S. is supported in part by an Alpha Omega Alpha Carolyn L. Kuckein Student Research Fellowship. I.W. is part of the Wayzata High Schools Honors Mentor Connection Program in Minnesota. M.O. is supported by the University of Minnesota Undergraduate Research Opportunities Program (UROP). I.M.S. is supported by an American Association for Cancer Research (AACR) Pancreatic Cancer Action Network Career Development Award ( 17-20-25-STRO ), an Institutional Research Grant ( 124166-IRG-58-001-55-IRG65 ) from the American Cancer Society , and support from the Masonic Cancer Center ( University of Minnesota Medical School ).

Funding Information:
We thank Dr. Pamela Rosato for help generating the CB tetramer. We thank the NIH Tetramer Core for generously supplying us with fluorescently labeled Ova257?264:H-2Kb tetramer. We thank Dr. Jason Mitchell at the Center for Immunology (CFI) for initial help with microscopy. We thank colleagues at the CFI at the University of Minnesota for helpful discussions. A.L.B. is supported by a computational training award from the American Association of Immunologists. E.J.S. is supported in part by an Alpha Omega Alpha Carolyn L. Kuckein Student Research Fellowship. I.W. is part of the Wayzata High Schools Honors Mentor Connection Program in Minnesota. M.O. is supported by the University of Minnesota Undergraduate Research Opportunities Program (UROP). I.M.S. is supported by an American Association for Cancer Research (AACR) Pancreatic Cancer Action Network Career Development Award (17-20-25-STRO), an Institutional Research Grant (124166-IRG-58-001-55-IRG65) from the American Cancer Society, and support from the Masonic Cancer Center (University of Minnesota Medical School). I.M.S. and A.L.B. designed the study, analyzed the data, and wrote the manuscript. A.L.B. E.S. J.F.R. I.W. and M.O. conducted experiments and analyzed data. I.M.S. supervised the study and is guarantor of the study. The authors declare no competing interests.

Publisher Copyright:
© 2019 The Author(s)

Keywords

PD-1
PD-L1
PDA
T cells
acquired resistance
immunotherapy
neoepitope
pancreatic cancer

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Combination PD-1 and PD-L1 Blockade Promotes Durable Neoantigen-Specific T Cell-Mediated Immunity in Pancreatic Ductal Adenocarcinoma",

abstract = "Burrack et al. investigate tumor-specific T cells during immunotherapy of pancreas cancer. T cells accumulate intratumorally yet rapidly exhaust. Combined PD-1 + PD-L1 blockade promotes peripheral T cell expansion, TNFα production, and eradication of spontaneous tumor recurrence in 50% of animals. Tumor variants defective in IFNγ-inducible Tap1 and MHC class I ultimately emerge.",

keywords = "PD-1, PD-L1, PDA, T cells, acquired resistance, immunotherapy, neoepitope, pancreatic cancer",

author = "Burrack, {Adam L.} and Spartz, {Ellen J.} and Raynor, {Jackson F.} and Iris Wang and Margaret Olson and Stromnes, {Ingunn M.}",

note = "Funding Information: We thank Dr. Pamela Rosato for help generating the CB tetramer. We thank the NIH Tetramer Core for generously supplying us with fluorescently labeled Ova 257–264 :H-2K b tetramer. We thank Dr. Jason Mitchell at the Center for Immunology (CFI) for initial help with microscopy. We thank colleagues at the CFI at the University of Minnesota for helpful discussions. A.L.B. is supported by a computational training award from the American Association of Immunologists . E.J.S. is supported in part by an Alpha Omega Alpha Carolyn L. Kuckein Student Research Fellowship. I.W. is part of the Wayzata High Schools Honors Mentor Connection Program in Minnesota. M.O. is supported by the University of Minnesota Undergraduate Research Opportunities Program (UROP). I.M.S. is supported by an American Association for Cancer Research (AACR) Pancreatic Cancer Action Network Career Development Award ( 17-20-25-STRO ), an Institutional Research Grant ( 124166-IRG-58-001-55-IRG65 ) from the American Cancer Society , and support from the Masonic Cancer Center ( University of Minnesota Medical School ). Funding Information: We thank Dr. Pamela Rosato for help generating the CB tetramer. We thank the NIH Tetramer Core for generously supplying us with fluorescently labeled Ova257?264:H-2Kb tetramer. We thank Dr. Jason Mitchell at the Center for Immunology (CFI) for initial help with microscopy. We thank colleagues at the CFI at the University of Minnesota for helpful discussions. A.L.B. is supported by a computational training award from the American Association of Immunologists. E.J.S. is supported in part by an Alpha Omega Alpha Carolyn L. Kuckein Student Research Fellowship. I.W. is part of the Wayzata High Schools Honors Mentor Connection Program in Minnesota. M.O. is supported by the University of Minnesota Undergraduate Research Opportunities Program (UROP). I.M.S. is supported by an American Association for Cancer Research (AACR) Pancreatic Cancer Action Network Career Development Award (17-20-25-STRO), an Institutional Research Grant (124166-IRG-58-001-55-IRG65) from the American Cancer Society, and support from the Masonic Cancer Center (University of Minnesota Medical School). I.M.S. and A.L.B. designed the study, analyzed the data, and wrote the manuscript. A.L.B. E.S. J.F.R. I.W. and M.O. conducted experiments and analyzed data. I.M.S. supervised the study and is guarantor of the study. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2019 The Author(s)",

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Combination PD-1 and PD-L1 Blockade Promotes Durable Neoantigen-Specific T Cell-Mediated Immunity in Pancreatic Ductal Adenocarcinoma

Abstract

Bibliographical note

Keywords

UN SDGs

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