Human breast tumor-infiltrating CD8+ T cells retain polyfunctionality despite PD-1 expression

Colt A. Egelston, Christian Avalos, Travis Y. Tu, Diana L. Simons, Grecia Jimenez, Jae Y. Jung, Laleh Melstrom, Kim Margolin, John H. Yim, Laura Kruper, Joanne Mortimer and Peter P. Lee ()
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Colt A. Egelston: Beckman Research Institute of City of Hope
Christian Avalos: Beckman Research Institute of City of Hope
Travis Y. Tu: Beckman Research Institute of City of Hope
Diana L. Simons: Beckman Research Institute of City of Hope
Grecia Jimenez: Beckman Research Institute of City of Hope
Jae Y. Jung: Norton Cancer Institute
Laleh Melstrom: Beckman Research Institute of City of Hope
Kim Margolin: Beckman Research Institute of City of Hope
John H. Yim: Beckman Research Institute of City of Hope
Laura Kruper: Beckman Research Institute of City of Hope
Joanne Mortimer: Beckman Research Institute of City of Hope
Peter P. Lee: Beckman Research Institute of City of Hope

Nature Communications, 2018, vol. 9, issue 1, 1-11

Abstract: Abstract Functional CD8+ T cells in human tumors play a clear role in clinical prognosis and response to immunotherapeutic interventions. PD-1 expression in T cells involved in chronic infections and tumors such as melanoma often correlates with a state of T-cell exhaustion. Here we interrogate CD8+ tumor-infiltrating lymphocytes (TILs) from human breast and melanoma tumors to explore their functional state. Despite expression of exhaustion hallmarks, such as PD-1 expression, human breast tumor CD8+ TILs retain robust capacity for production of effector cytokines and degranulation capacity. In contrast, melanoma CD8+ TILs display dramatic reduction of cytokine production and degranulation capacity. We show that CD8+ TILs from human breast tumors can potently kill cancer cells via bi-specific antibodies. Our data demonstrate that CD8+ TILs in human breast tumors retain polyfunctionality, despite PD-1 expression, and suggest that they may be harnessed for effective immunotherapies.

Date: 2018
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DOI: 10.1038/s41467-018-06653-9

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