title: IL-10 enhances CTL-mediated tumor rejection by inhibiting highly suppressive CD4+T cells and promoting CTL persistence in a murine model of plasmacytoma.
abstract: 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 inIL-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-γ-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.
authors.affiliation: Department of Hematology; Chinese Navy General Hospital ; Beijing, China ; Department of Pathology and Comprehensive Cancer Center; The Ohio State University Medical Center ; Columbus, OH USA ; Department of Hematology; Chinese PLA General Hospital ; Beijing, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology and Comprehensive Cancer Center; The Ohio State University Medical Center ; Columbus, OH USA.
authors.forename: Jin-Qing
authors.initials: JQ
authors.lastname: Liu
authors.affiliation: Department of Pathology and Comprehensive Cancer Center; The Ohio State University Medical Center ; Columbus, OH USA.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Talebian
authors.affiliation: Department of Pathology and Comprehensive Cancer Center; The Ohio State University Medical Center ; Columbus, OH USA.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Hematology; Chinese PLA General Hospital ; Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Pathology and Comprehensive Cancer Center; The Ohio State University Medical Center ; Columbus, OH USA.
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Bai
keywords: CD4+ T cells; CTL, cytotoxic T lymphocytes; IL-10, interleukin 10; MHC, major histocompatibility complex; Rag, recombination-activating gene; TCR, T cell receptor; Th17; cytotoxic T lymphocytes; interleukin 10; regulatory T cells