Dendritic Cell-derived Interleukin-27Plays Both Anti-tumor And Immunosuppressive Roles In Tumor Microenvironment

IL-27, comprised of IL-27p28and EBI3two subsets, is a new member of IL-12family. IL-27has been reported to play important roles in both innate and adaptive immune responses. But the functions of endogenous IL-27in tumor microenvironment are still unclear. In our research, we used IL-27p28conditional knockout mice to find out how IL-27regulated tumor infiltrating lymphocytes. Tumor sizes of B16melanoma and MCA-induced fibrosarcoma significantly increased in IL-27p28knockout mice, although IL-27did not directly influence tumor cell proliferation in vitro. Thus we suggested that IL-27played roles in tumor growth by regulating immune system in tumor. We found tumor killing NK and NKT cells significantly decreased in tumor site, and tumor killing factors IFN-y and perform produced by NK and NKT cells also reduced. As an important chemokine regulating NK and NKT cells recruitment, CXCL10decreased in tumor microenvironment of IL-27p28knockout mice, leading to NK and NKT cells reduction in tumor site. Lack of CXCL10also attenuated IFN-y produced by NK and NKT cells, at the same time, decrease of IFN-y could also attenuate CXCL10produced by MDSCs. In addition, IFN-y inducer IL-12secreted by DCs decreased in IL-27p28knockout mice. Therefore, decrease of CXCL10, IL-12and IFN-y destroyed the anti-tumor abilities of NK and NKT cells, leading to acceleration of tumor growth. Interestingly, percentage of Treg also decreased in tumor microenvironment of IL-27p28knockout mice, because that DC-derived Treg recruiting chemokine CCL22decreased in tumor site. Treg reduction resulted in more IFN-y production by CD4+T cells. All in all, IL-27plays both positive and negative roles in tumor microenvironment, indicating that IL-27involves in cancer immunoediting process. We should enhance the positive roles and inhibit the negative roles of IL-27in cancer therapy.