IL-10 enhances CTL-mediated tumor rejection by inhibiting highly suppressive CD4+ T cells and promoting CTL persistence in a murine model of plasmacytoma

Oncoimmunology. 2015 May 13;4(7):e1014232. doi: 10.1080/2162402X.2015.1014232. eCollection 2015 Jul.


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-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.

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.

Publication types

  • Research Support, N.I.H., Extramural