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

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.