期刊
ONCOIMMUNOLOGY
卷 4, 期 7, 页码 -出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2015.1014232
关键词
CD4(+) T cells; cytotoxic T lymphocytes; interleukin 10; regulatory T cells; Th17
资金
- National Cancer Institute [R01CA138427]
Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine that regulates immune responses. IL-10 has also been shown to enhance antitumor CD8(+) T-cell responses in tumor models although the underlying mechanisms are not fully understood. In this study, we used a series of genetic mouse models and the mouse plasmacytoma J558 model to investigate this issue. J558 tumors grew significantly faster in IL-10(-/-) mice than in wild type (WT) mice, but similarly in IL-10(-/-) Rag2(-/-) and Rag2(-/-) mice. Tumors from IL-10(-/-) mice contained fewer IFN-gamma-producing CD8(+) and CD4(+) T cells than tumors from WT mice. Strikingly, depletion of total CD4(+) T cells, but not CD25(+) cells, resulted in tumor eradication in IL-10(-/-) mice. Adoptive transfer studies revealed that CD4(+) T cells from IL-10(-/-) mice exhibited more potent suppression of cytotoxic T lymphocyte (CTL)-mediated tumor rejection than their WT counterparts, and IL-10-deficient tumor-infiltrating CD4(+) T cells expressed higher levels of PD-L1 and CTLA-4 inhibitory molecules. Although IL-10-deficient CD8(+) T cells are not defective in activation and initial rejection of tumors, adoptive transfer studies using IL-10-deficient P1CTL transgenic T cells that recognize the tumor rejection antigen P1A reveal that IL-10 is required for long-term persistence of CTLs and control of tumor growth. Thus, we have found that IL-10 enhances antitumor CTL responses by inhibiting highly suppressive CD4(+) T cells and promoting CTL persistence. These data have important implications for the design of immunotherapy for human cancer.
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