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J Immunol. 2017 Apr 1;198(7):2979-2988. doi: 10.4049/jimmunol.1601064. Epub 2017 Feb 15.

Virus-Specific CD8+ T Cells Infiltrate Melanoma Lesions and Retain Function Independently of PD-1 Expression.

Author information

1
Department of Microbiology and Immunology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107.
2
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, 4710-057 Braga, Portugal; and.
3
ICVS/3Bs, PT Government Associated Laboratory, 4710-057 Braga/Guimarães, Portugal.
4
Department of Microbiology and Immunology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107; christopher.snyder@jefferson.edu.

Abstract

It is well known that CD8+ tumor-infiltrating lymphocytes (TILs) are correlated with positive prognoses in cancer patients and are used to determine the efficacy of immune therapies. Although it is generally assumed that CD8+ TILs will be tumor-associated Ag (TAA) specific, it is unknown whether CD8+ T cells with specificity for common pathogens also infiltrate tumors. If so, the presence of these T cells could alter the interpretation of prognostic and diagnostic TIL assays. We compared TAA-specific and virus-specific CD8+ T cells in the same tumors using murine CMV, a herpesvirus that causes a persistent/latent infection, and vaccinia virus, a poxvirus that is cleared by the host. Virus-specific CD8+ TILs migrated into cutaneous melanoma lesions during acute infection with either virus, after a cleared vaccinia virus infection, and during a persistent/latent murine CMV infection. Virus-specific TILs developed independently of viral Ag in the tumor and, interestingly, expressed low or intermediate levels of full-length PD-1 in the tumor environment. Importantly, PD-1 expression could be markedly induced by Ag but did not correlate with dysfunction for virus-specific TILs, in sharp contrast to TAA-specific TILs in the same tumors. These data suggest that CD8+ TILs can reflect an individual's immune status, rather than exclusively representing TAA-specific T cells, and that PD-1 expression on CD8+ TILs is not always associated with repeated Ag encounter or dysfunction. Thus, functional virus-specific CD8+ TILs could skew the results of prognostic or diagnostic TIL assays.

PMID:
28202614
PMCID:
PMC5360480
DOI:
10.4049/jimmunol.1601064
[Indexed for MEDLINE]
Free PMC Article

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