Journal
CANCER IMMUNOLOGY RESEARCH
Volume 7, Issue 6, Pages 1013-1024Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2326-6066.CIR-18-0504
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Funding
- Swiss National Science Foundation [Sinergia CRSII3_141879, Sinergia CRSII3_160708, 31003A_156469]
- ERC (PROTECTC)
- Van Andel Research Institute
- Phi Beta Psi Sorority
- Swiss National Science Foundation (SNF) [31003A_156469] Funding Source: Swiss National Science Foundation (SNF)
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microRNAs are short noncoding RNAs that regulate protein expression posttranscriptionally. We previously showed that miR-155 promotes effector CD8(+) T-cell responses. However, little is known about the regulation of miR-155 expression. Here, we report that antigen affinity and dose determine miR-155 expression in CD8(+) T cells. In B16 tumors expressing a low-affinity antigen ligand, tumor-specific infiltrating CD8(+) T cells showed variable miR-155 expression, whereby high miR-155 expression was associated with more cytokine-producing cells and tumor control. Moreover, anti-PD-1 treatment led to both increased miR-155 expression and tumor control by specific CD8(+) T cells. In addition, miR-155 overexpression enhanced exhausted CD8(+) T-cell persistence in the LCMV cl13 chronic viral infection model. In agreement with these observations in mouse models, miR-155 expression in human effector memory CD8(+) T cells positively correlated with their frequencies in tumor-infiltrated lymph nodes of melanoma patients. Low miR-155 target gene signature in tumors was associated with prolonged overall survival in melanoma patients. Altogether, these results raise the possibility that high miR-155 expression in CD8(+) tumor-infiltrating T cells may be a surrogate marker of the relative potency of in situ antigen-specific CD8(+) T-cell responses.
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