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

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.

Tumor‐Derived Peptidoglycan Recognition Protein 2 Predicts Survival and Antitumor Immune Responses in Hepatocellular Carcinoma

“…Intratumoral cluster of differentiation 3–positive (CD3 + ), CD8 + T‐cell infiltrates are predictive of response to immunotherapeutic interventions and associate favorably with patient survival . To analyze the essential relationship between the antitumor immune response and PGLYRP2 level in tumor tissues, quantitative assessment of CD3 and CD8 in paraffin‐embedded tumor tissue was performed using immunofluorescence assay.…”

Quantitative multiplex immunofluorescence analysis identifies infiltrating PD1+CD8+ and CD8+ T cells as predictive of response to neoadjuvant chemotherapy in breast cancer

“…Yet, PD1 + CD8 + TILs in human breast tumors has been reported to remain functional with high cytokine production and degranulation capacity. 24 TIM3 is also an inhibitory checkpoint that contributes to the immune suppressive microenvironment and can be a resistance mechanism to immunotherapy. Thus PD1 + or TIM3 + TILs may be predictive or prognostic in BC.…”

PD-1 receptor on immune cells, its expression and potential role in cancer therapy

“…In breast cancer, PD-1 expression in tumor-infiltrating CD8+ T cells was also increased. However, the intratumor T cells had different phenotype and functional properties, i.e, TIM-3 and 2B4 proved to be more expressed on CD8+ T cells from melanoma patients, whereas CD8+ T cells from breast cancer patients retained their degranulation ability, IFNγ, TNFα and IL-2 production, and could be therefore regarded as functional cell population [66]. Similar situation is noted for other malignant diseases including oncohematological diseases, e.g AML [67].…”