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Enhancement of Tumor Immunotherapy by Blockade of a Prostate Tumor Derived Immunosuppressive Factor

机译:通过阻断前列腺肿瘤来源的免疫抑制因子增强肿瘤免疫治疗

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SIit2 is a soluble protein that has been demonstrated to regulate cell migration and inhibit inflammatory reactions. Recent studies suggest that SIit2 may play a role in tumor development. However conflict results have been reported about the expression level of SIit2 in normal and tumor tissues and the effect of SIit2 on development. The current studies in this report have for the first time demonstrated that forced expression of SIit2 in tumors suppresses the growth of human prostate tumor Du145 fibrosarcoma HT1080 and epidermoid tumor A431 cells in an anchorage independent way. Further experiments indicate that SIit2 inhibits tumor growth and reduces metastasis of HT1080 tumors in lungs of nude mice. Additionally in situ detection of transcriptional level indicates that SIit2 is down regulated in human tumor samples compared to normal tissues that mostly express Slit2 mRNA. Since all three tumor cell lines in the current studies express Robo4 a receptor for SIit2 the suppressive effect of SIit2 on tumors is likely mediated by the interaction of Slit2 with the receptor. These data imply that SIit2 is a tumor suppressor which is down regulated during tumor development. The effect of SIit2 on tumorigenesis is largely unexplored and further studies are required to define the mechanism for SIti2 mediated suppression of tumors.

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