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

Mojgan Ahmadzadeh, Laura A. Johnson, Bianca Heemskerk, John R. Wunderlich, Mark E. Dudley, Donald E. White, Steven A. Rosenberg

Research output: Contribution to journalArticlepeer-review

Abstract

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 PD-1- TIL. Effector cytokine production by PD-1+ TIL was impaired compared with PD-1- TIL and PBL. Collectively, the phenotypic and functional characterizations of TIL revealed a significantly higher frequency and level of PD-1 expression on TIL compared with normal tissue T-cell infiltrates and PBL, and PD-1 expression correlated with an exhausted phenotype and impaired effector function. These findings suggest that the tumor microenvironment can lead to up-regulation of PD-1 on tumor-reactive T cells and contribute to impaired antitumor immune responses.

Original languageEnglish (US)
Pages (from-to)1537-1544
Number of pages8
JournalBlood
Volume114
Issue number8
DOIs
StatePublished - 2009
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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