Progress in tumor immunosuppression

Recently, Wan Xiaochun, a researcher of protein and cell medicine research center of Shenzhen Institute of advanced technology, Chinese Academy of Sciences, and his research team have made new progress in tumor immunosuppression research Relevant papers "TIPE2 specifies the functional polarization of myoid derived suppressor cells during tumorigenesis" were published online in the Journal of Experimental Medicine (DOI: 10.1084 / JEM 20182005) The first author is Yan Dehong, an assistant researcher The presence of myeloid derived suppressor cells (MDSCs) in tumor microenvironment is the main factor to form tumor immunosuppressive microenvironment and the key mechanism to weaken the effect of tumor immunotherapy Myeloid derived inhibitory cells are a group of heterogeneous cells, derived from bone marrow progenitor cells and immature myeloid cells, which are precursors of dendritic cells, macrophages and granulocytes A large number of MDSCs were amplified in the blood, spleen and tumor tissues of tumor bearing mice, as well as in the peripheral blood and tumor tissues of tumor patients MDSCs can inhibit the acquired and natural anti-tumor immunity of the body through various ways, make tumor cells escape the immune surveillance and attack of the body, and promote the occurrence and development of tumor Therefore, targeted blocking MDSCs to reverse the immunosuppressive state of tumor microenvironment is the key to enhance the effect of tumor immunotherapy Tumor necrosis factor - α - inducible protein 8-like-2 (TIPE2) is a kind of professional phosphoinositide second messenger transporter, which is specifically expressed in leukocytes and regulates the polarization changes in their migration process TIPE2 plays a role of molecular bridge in the process of inflammation and cancer transformation On the one hand, overexpression in tumor cells induces tumor cell death and suppresses tumor occurrence; on the other hand, it suppresses inflammation by negatively regulating TCR and TLR signals of T cells and macrophages to promote tumor occurrence However, whether TIPE2 can regulate the function of MDSCs in tumor immunosuppressive microenvironment is still unknown After in-depth study, Wan Xiaochun's team found that TIPE2 accelerated the polarization of MDSCs to tumor phenotype by up regulating the expression of C / EBP β, thus promoting tumor development However, MDSCs knocked out of TIPE2 lost its immunosuppressive function and delayed tumor progression and metastasis These results reveal that TIPE2 is a molecular switch that promotes the conversion between tumor MDSCs and anti-tumor MDSCs, and it is a new potential target of tumor immunotherapy.