期刊
JOURNAL OF IMMUNOLOGY
卷 198, 期 7, 页码 2979-2988出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1601064
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资金
- National Institutes of Health [R03 CA174979, R01 AI106810]
- American Cancer Society [ACS-IRG-08-060-04, RSG-15-184-01]
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 virusspecific 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. Virusspecific TILs developed independently of viral Ag in the tumor and, interestingly, expressed low or intermediate levels of fulllength 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.
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