| Tumor immune evasion plays an important role in the physiopathological process of tumor genesis, invasion and metastasis. Many reasons account for the occurrence of tumor immune evasion, for example, the tumor cell couldn't successfully present the antigen signal, or the tumor cells could counteract the host immune attaction, or even the host immune system presents certain immune defection/inhibition. In regard, the contribution of the costimulatory molecule as well as its regulating net in tumor immune evasion have sparked growing interest within the past decade. In brief, the costimulatory molecules could be predominantly divided into two super families, namely B7/CD28 and TNF/TNFR. The signal pathway mediated by the costimulatory molecules as well as their receptors essentially led to the activation of na?ve T cells and the regulation of immune functions of activated T cells. The classic B7 family signal pathway was first found to activate the na?ve T cells, but emerging evidences have support that these molecules could also affect the sensitized T lymphocytes and negatively regulate the immune response. Among these costimulatory molecules, it has been demonstrated that B7-H1 and B7-H3 expressed in a wide spectrum of human cancers, and roled importantly in the tumor immune response. In the present study, on one hand, we carried out the immunohistochemistry to characterize the B7-H1 and B7-H3 expression in 102 human colorectal carcinomas, and then analyzed their correlations to patients'clinical parameters as well as the infiltrating intensities of T lymphocytes immunolabled by anti-CD3 antibody; on the other hand, we further investigated the potential mechanism of the cellular regulation of B7-H1 and B7-H3 expression involed in tumorenvioroment in a series of colorectal cancer cell lines.Our results indicated that the costimulatory molecules B7-H1 and B7-H3 highly expressed in human colorectal cacners and predominantly expressed in the plasma and membrane of cancer cells, while they were undeted or slightly expressed in adjacent normal tissues. The B7-H1 expression in colorectal cancers was significantly correlated to the tumor location (P<0.05), but was not correlated to other parameters. The B7-H3 expression in colorectal cancers was significantly correlated to tumor stage (P<0.05), mucus adenocarcinoma status (P<0.05), but not correlated to other clinical parameters. The B7-H1 expression in colorectal cancers was negatively correlated to the intensity of T lymphocytes infiltrating (tumor stroma, P<0.05; tumor nest, P<0.0001); and the B7-H3 expression in colorectal cancers was also negatively correlated to the intensity of T lymphocytes infiltrating (tumor stroma, P<0.05; tumor nest, P<0.05). The B7-H1 expression in colorectal cancers was positively correlated to the B7-H3 expression (P<0.0001), moreover, the group including the cases with both B7-H1 and B7-H3 high expession represented with lower T lympocytes infiltrating than those with both low exression group (P<0.0001) and those with either high expression group (P<0.05). Flow cytometry revealed that no expression of membranous B7-H1 was found in colorectal cancer cell lines LS174T, Caco-2, Colo-320, SW-480, CW-2, while it could be up-regulated by IFN-γbut not TNF-α. Membranous B7-H3 expression was widely found in all the five colorectal cancer cell lines, and neither IFN-γnor TNF-αstimulation could alter its expression level. Interestingly, soluble B7-H3 secretion was significantly up-regulated by either IFN-γor TNF-αstimulation (P<0.001), in response to which could be inhibited by MMPI (P<0.001), which suggested that the generation of soluble B7-H3 molecules was associated with the cleavage of MMP. Moreover, we also found that the soluble B7-H3 in the serum from CRC patients was significantly increased in constrast to that from the health donors (P<0.0001).In conclusion, we hereby first reported the expression and clinical significance of the costimulatory molecules B7-H1 and B7-H3 in human colorectal cancers, which suggested that both B7-H1 and B7-H3 expression in colorectal cancers played an important role in the development of colorectal carcinoma and negatively regulated the T lymphocytes-mediated anti-tumor immune response. The co-stimulatory molecules B7-H1 and B7-H3 might be novel biological markers and of great clincal use in the diagnosis and prognositic prediction of colorectal cancers. Moreover, both membranous and soluble B7-H3 molecules take part in the tumor invasion of colorectal cancers. In future, considerable efforts are needed to improve current therapeutic modalities and to explore novel therapeutic interventions targeting the co-stimulatory molecules B7-H1 and B7-H3 in the clinical treatment of colorectal cancers.
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