Oct 18, 2018

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

Nature Communications
Colt A EgelstonPeter P Lee

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.

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Mentioned in this Paper

PTK6 gene
T-Lymphocyte
Tumor Necrosis Factor-alpha
Suppressor T-Lymphocytes, CD8-Positive
Neoplasms
Cell Degranulation
CD8-Positive T-Lymphocytes
Cell Differentiation Process
Melanoma vaccine
Infiltration

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