IL-10 elicits IFNγ-dependent tumor immune surveillance

Cancer Cell. 2011 Dec 13;20(6):781-96. doi: 10.1016/j.ccr.2011.11.003.

Abstract

Tumor immune surveillance and cancer immunotherapies are thought to depend on the intratumoral infiltration of activated CD8(+) T cells. Intratumoral CD8(+) T cells are rare and lack activity. IL-10 is thought to contribute to the underlying immune suppressive microenvironment. Defying those expectations we demonstrate that IL-10 induces several essential mechanisms for effective antitumor immune surveillance: infiltration and activation of intratumoral tumor-specific cytotoxic CD8(+) T cells, expression of the Th1 cytokine interferon-γ (IFNγ) and granzymes in CD8(+) T cells, and intratumoral antigen presentation molecules. Consequently, tumor immune surveillance is weakened in mice deficient for IL-10 whereas transgenic overexpression of IL-10 protects mice from carcinogenesis. Treatment with pegylated IL-10 restores tumor-specific intratumoral CD8(+) T cell function and controls tumor growth.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Breast Neoplasms / metabolism
  • CD8-Positive T-Lymphocytes / enzymology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Line, Tumor
  • Cytotoxicity, Immunologic
  • Female
  • Granzymes / metabolism
  • Humans
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism*
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology
  • Interleukin-10 / metabolism*
  • Interleukin-10 Receptor alpha Subunit / genetics
  • Interleukin-10 Receptor alpha Subunit / metabolism
  • Mammary Neoplasms, Experimental / blood supply
  • Mammary Neoplasms, Experimental / drug therapy
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neoplasm Transplantation
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / immunology*
  • Neoplasms, Experimental / pathology
  • Perforin / metabolism
  • Skin Neoplasms / chemically induced
  • Skin Neoplasms / immunology
  • Skin Neoplasms / pathology
  • Spleen / metabolism
  • Transplantation, Heterologous
  • Tumor Burden
  • Tumor Escape

Substances

  • Antineoplastic Agents
  • IL10 protein, human
  • Interleukin-10 Receptor alpha Subunit
  • Perforin
  • Interleukin-10
  • Interferon-gamma
  • Granzymes
  • Gzmb protein, mouse

Associated data

  • GEO/GSE30710