Egelston et al. analyzed PD-1 and other phenotypic markers in human breast cancer (mostly ER+/HER2-) and melanoma and observed that CD8+ TILs from both tumor types were primarily CCR7-/CD45RA- effector memory cells displaying a seemingly exhausted Eomes+/TIGIT+/2B4+ and terminally differentiated CD127-/KLRG1- profile. However, breast cancer PD-1+CD8+ TILs showed enhanced IFNγ, TNFα, and IL-2 production and stronger cytolytic capability in conjunction with a bispecific antibody compared to same cells derived from melanoma. These results reveal a more nuanced relationship between PD-1 expression and T cell exhaustion.
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.
Author Info: (1) Department of Immuno-Oncology, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA. (2) Department of Immuno-Oncology, Beckman Research Institute of City of Hope
Author Info: (1) Department of Immuno-Oncology, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA. (2) Department of Immuno-Oncology, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA. (3) Department of Immuno-Oncology, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA. (4) Department of Immuno-Oncology, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA. (5) Department of Immuno-Oncology, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA. (6) Department of Dermatologic Oncology, Norton Cancer Institute, Louisville, KY, 40202, USA. (7) Department of Surgery, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA. (8) Department of Medical Oncology, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA. (9) Department of Surgery, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA. (10) Department of Surgery, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA. (11) Department of Medical Oncology, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA. (12) Department of Immuno-Oncology, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA. plee@coh.org.
