IL-10 Elicits IFNγ-Dependent Tumor Immune Surveillance

Mumm, J.B., et al., 2011. Cancer Cell. 20: 781-796

Speaker: Ming-Zhang Lin (林明璋)                              Time: 15:10~16:00, May. 23, 2011

Commentator: Chiou-Feng Lin (林秋烽博士)             Place: Room 601

Abstract:

Activation of CD8⁺ T Cells in the tumor is essential tumor immune surveillance , but in some cancer are limited intratumoral CD8⁺ T cells activity and lead to immune evasion of human and mouse tumors. IL-10 is thought to contribute to the underlying immune suppressive microenvironment. It is produced primarily by monocytes and to a lesser extent by lymphocytes. This cytokine has pleiotropic effects in immunoregulation and inflammation. It down-regulates the expression of Th1 cytokines, MHC class II antigens, and costimulatory molecules on macrophages. It has also been demonstrated that IL-10 can impair secondary CD8⁺ T cell responses. Previous study indicated that IL-10 may be an important growth factor for cancer cells and also contribute tumor immune evasion . Contrarily, some study found that local release of IL-10 by transfected mouse mammary adenocarcinoma cells does not suppress but enhances antitumor reaction and elicits a strong cytotoxic lymphocyte and antibody-dependent immune memory. However, the relationship between IL-10 and tumor it’s not fully clarified . In this study they screening a large number of immune modulating cytokines for an influence on the growth of tumors in immune competent mice, the author confirmed the strong antitumor activity of IL-10. They also defied those expectations the demonstrate that IL-10 induces several essential mechanisms for effective antitumor immune surveillance: IL-10 induces antigen-specific CD8⁺ T cell responses in tumor-bearing mice also elevates IFNγ and granzymes. Consequently, tumor immune surveillance is weakened in mice deficient for IL-10. Treatment with PEG IL-10 restores tumor specific intratumoral CD8⁺  T cell function and major histocompatibility complex expression that controls tumor growth.

References:

1.      Moore, K.W., et al., Interleukin-10 and the interleukin-10 receptor.  Immunol. 19, 683–765.

2.      M ,Giovarelli., et al., Local release of IL-10 by transfected mouse mammary adenocarcinoma cells does not suppress but enhances antitumor reaction and elicits a strong cytotoxic lymphocyte andantibody-dependent immune memory. J. Immunol. 155:3112–23