Tumor antigen–specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired

Tumor antigen-specific T cells are found within melanomas, yet tumors continue to grow. Although the tumor microenvironment is thought to influence the suppression of tumor-reactive T cells, the underlying mechanisms for this T-cell dysfunction are not clear. Here, we report that the majority of tumor infiltrating T lymphocytes (TIL), including MART-1/Melan-A melanoma antigen-specific CD8 T cells, predominantly expressed PD-1, in contrast to T cells in normal tissues and peripheral blood T lymphocytes (PBL). PD-1(+) TIL expressed CTLA-4 and Ki-67, markers that were not expressed by PD-1(-) TIL and T cells in the normal tissues and PBL. Moreover, PD-1(+) TIL were primarily HLA-DR(+) and CD127(-), in contrast to…