Study On The Functions Of IL-17D In Cancer Progression

Objective: Cancer is a broad group of diseases involving unregulated cellgrowth. According to the data published by World Health Organization(WHO), approximately8.2million people worldwide died of cancer in2012.In China, the cancer incidence of residents is285.91/100000, death caused bycancer accounted for13%of the total death. Rapid progression is a feature ofcancer, and the progression of cancer is regulated by many factors in vivo, andinnate immunity is one of the most important factor. Innate immunity can be adouble-edged sword in cancer progression, certain types of immune cells frominnate immune system can inhibit cancer progression, in contrast, other typesof immune cells can enhance cancer progression. Interleukin are a groupof cytokines that were first seen to be expressed by white blood cells, andrecent studies showed that interleukin can be expressed by multiple types ofcell. Interleukin can regulate immune system by affecting immune cellsproliferation, differentiation, recruitment, and stimulate/inhibit immune cellsto product certain cytokines. In a recent study, IL-17D was proofed to be ableto stimulate endothelial cells to produce immunity related cytokines andchemokine including IL-6, IL-8and GM-CSF. It showed that IL-17D haspotential function of regulating cancer progression by manipulating innateimmune system. Our study aims to investigate if IL-17D can regulate cancerprogression by manipulating innate immunity in the absence of adaptiveimmunity, and further discuss the mechanism of IL-17D manipulating innateimmunity. To confirm the function of IL-17D in cancer progression andprovide theoretical evidence of cancer immune therapy.Methods: In this study,2IL-17D over expressed ovarian cancer cell lines,HTB-77(IL-17D) and HTB-161(IL-17D), and2IL-17D normal expressedovarian cancer cell lines, HTB-77(Ctrl) and HTB-161(Ctrl), were made by virus transduction based on2parent ovarian cell lines, which are HTB-77andHTB-161. In vitro and in vivo experiment were performed to investigate if andhow IL-17D can regulate cancer progression. And flow-cytometry techniquewas used to detect percentage of different immune cell types in tumor tissue,to investigate the mechanism of IL-17regulate cancer progression.Statistical analysis was performed by using SPSS ver.13.0. To show Thetumor-free survival time of mice injected by ovarian cancer cell lines withdifferent IL-17D expression level were compared by using analysis ofvariance. And t test was used to compare the recruitment of immune cells(CD45+), M1/M2macrophages, neutrophils (including N1/N2neutrophils)and dendritic cells between IL-17D over expressed ovarian cancer tissues andIL-17D normal expressed ovarian cancer tissues. A probability level of5%was considered significant.Results:1Ovarian cancer cell lines transduced by virus with IL-17D gene showeda significant higher level of IL-17D expression than parent cell lines, and celllines transduced by virus with control gene showed no difference of IL-17Dexpression than parent cell lines.2Cell culture showed different IL-17D expression has no effect on cellproliferation of ovarian cancer cells in vitro.3In animal experiment, IL-17D over expressed ovarian cells showed amore rapidly progression than IL-17D normal expressed ovarian cells in theabsence of adaptive immunity.4Flow cytometry showed there’s no difference of immune cell (CD45+)percentage in total cell between IL-17D over expressed ovarian cancer tissueand control ovarian cancer tissue. M1macrophage percentage in total immunecell and dendritic cell percentage in total immune cell are significantlydecreased in IL-17D over expressed ovarian cancer tissue than control group.Neutrophils (including N1/N2neutrophils) is increased in IL-17D overexpressed ovarian cancer tissue than control group. Conclusion: In the absence of adaptive immunity, IL-17D exhibit theability to enhance cancer progression by manipulating intratumoral immunecell recruitment, with decreasing M1macrophage recruitment, increasingneutrophils (including N1/N2neutrophils) cell recruitment.