Costimulatory molecule CD_(40) is extensively expressed by immune, hematopoietic, epithelial, and a wide range of tumor cells. As a potential target for novel cancer therapy, CD_(40)/CD_(40L) may mediate tumor regression through both an indirect effect of immune activation and a direct cytotoxic effect on the tumor. Several drug formulations that target the CD_(40)/CD_(40L) pathway have undergone phase I clinical evaluation in advanced-stage cancer patients, and initial findings show objective clinical responses immune modulation function and have not serious toxicity.

Th17 cells are CD4 + effector T cells.Many studies have confirmed that Th17 cells and their related cytokines exist in many kinds of tumors,and play critical roles in inflammation related tumors.But the expression and differentiation in tumor microenvironment,the immune regulation mechanisms and functional effects of Th17 cells remains controversial.

Objective:To accumulate dendritic cells(DC) into the peripheral blood and induce the specific cytotoxic T lymphocyte against tumor.Methods:B220~-CD11c~+ cells were sorted from the peripheral blood of C57BL/6 mice injected i.v.with P.acnes,and cultured for about six days in the presence of GM-CSF,IL-4 and mTNF-?.Phenotype and mixed leukocyte reaction(MLR) of these cells were assayed.CTL to anti-tumor,which was developed by cultured B220~CD11c~+ cells loading tumor antigen,was detected.Results:B220~-CD11c~+ cells were rapidly accumulated in the circulation of the mice after P.acnes injection.These cells could differentiate into mature DC when cultured in the presence of cytokines for several days.Moreover,cultured B220~-CD11c~+ cells loading tumor antigen could stimulate naive splenic CD3~+T cells generate high level of IFN-? and tumor specific cytolytic reactivity in vitro.Conclusion:B220~-CD11c~+ DC precursors rapidly accumulated in the peripheral blood after injection of(P.acnes) in mice.T cells could develop specific CTL to anti-target tumor cells in vitro when stimulated with P.acnes-mobilized DC loading tumor antigen.

Objective CD4 +IL-17 +cells are a group of newly discovered effector CD4 +T cells, which may play a key role in the pathogenesis of cancer.This study aims to investigate the expres-sion of CD4 +IL-17 +cells in pancreatic cancer and its correlation with the clinicopathological characteristics and prognosis of the dis-ease as well as the clinical significance of the cells in the microenvironment of pancreatic cancer. Methods We collected tumor tis-sue and tumor-adjacent normal tissue samples from 51 pancreatic cancer patients.We determined the expressions of CD34 and vascular endothelial growth factor ( VEGF) and measured the proportion of IL-17 +cells in the cancer tissue using immunohistochemistry and the fluorescence activated cell sorter, respectively, followed by analysis of their correlation with tumor angiogenesis, clinicopathological pa-rameters, and survival time of the patients. Results The percentage of CD4 +IL-17 +cells in tumor tissue was positively correlated with microvessel density (r =0.534, P<0.05) and the expression of VEGF in the tumor tissue (r=0.356, P<0.05).IL-17 +cells were expressed more highly in the tumorous than in the tumor-adjacent normal tissue (P<0.05), and the expression level was correla-ted with the stage of tumor, node, and metastasis (TNM) and lymph node metastasis (P<0.05), but not with the patients′gender or age, tumor size, tumor location, histological grade, or local invasion (P>0.05).Fifty (98.0%) of the patients were successfully followed up for 2-67 months, which revealed a median survival time of 16.6 ±4.8 months, significantly longer in those with a higher expression of intratumoral IL-17 +cells (P<0.05).Univariate analysis showed an association of the survival rate with the tumor size, TNM stage, lymph node metastasis, and level of intratumoral IL-17 +cells, while multivariate analysis showed the TNM stage to be an independent prognostic factor for the survival of the pancreatic cancer patients. Conclusion The expression of CD4 +IL-17 +cells in the tumor tissue is positively correlated with tumor angiogenesis, while that of IL-17 +cells with the clinicopathological parameters and survival time of the patients and therefore may serve as an important immune indicator for the prognosis of pancreatic cancer.