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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 16, 2018
- Source ID
- 10.1038/s41467-018-06653-9
Entities
People
- Christian Avalos
- Colt Egelston
- Diana L. Simons
- Grecia Jimenez
- Jae Y. Jung
- Joanne Mortimer
- John H. Yim
- Kim Margolin
- Laleh Melstrom
- Laura Kruper
- Peter P Lee
- Travis Y Tu
Organizations
- National Cancer Institute
- Stand Up to Cancer
- The Breast Cancer Research Foundation
- United States Department of Defense