An Investigation Of B7-H4Expression And It’s Correlation With The Infiltrating T Lymphocyte Subtypes In Human Cervical Cancers

Objective: To investigate B7-H4expression and it’s correlation withthe number of tumor-infiltrating T lymphocytes and their cytokine secretionin human cervical cancers. To study the immune regulatory effect ofrecombinant human B7-H4protein on cell cycle, apoptosis and cytokinesecretion of active T lymphocytes of cervical cancer patients peripheralblood in vitro.Methods: B7-H4expression was detected in30cases of normal humancervical tissue,30cases of CINII-III, and67cases of cervical cancer byimmunohistochemistry SP staining. Tumor-infiltrating Foxp3~+T, CD4~+T andCD8~+T lymphocytes, and their secretion of TGF-β1and IFN-γ in cervicalcancer tissues were detected by indirect immunofluorescent double-staining.After the activated peripheral blood T lymphocytes were co-cultured withB7-H4for48h, their cell-cycle, apoptosis and T cells subtypes were detectedby FCM. Cytokine concentration in the culture supernatant was determinedby ELISA microarray. Result: B7-H4did not express in normal cervical tissue, but it faintlyexpressed in part epithelium of CINII-III, and expressed in46%（31/67） cervical cancers. There was significant difference of B7-H4expression between cervical cancers with normal cervical tissue andCINII-III (p<0.01, p<0.05).The number of tumor-infiltrating CD8~+Tlymphocytes and their IFN-γ secretion in B7-H4positive expression cervicalcancers was significantly lower than that of B7-H4negative cases (p<0.001,p<0.035). There was no difference of tumor-infiltrating FOXP3~+lymphocytes, CD4~+T lymphocytes and TGF-β1secretion between B7-H4positive cervical cancers with that of B7-H4negative cases(p>0.05, p>0.05).After cervical cancer patients’ activated T cells were co-cultured with B7-H4for48h, the cells of G, G2and S phase were90.59%,8.55%and0.87%, thatof blank group were92.83%,6.09%and1.13%; the Ki67positive rates ofCD4~+T and CD8~+T cells were2.13%±0.13%and1.03%±1.33%, they werelower than that of blank group (2.74%±0.98%and1.71%±1.32%). B7-H4decreased the proportion of CD4~+T and CD8~+T cells in CD3~+T cells, but therate of CD4~+T/CD8~+T and the proportion of CD4~+CD25~+Foxp3~+T cellsincreased, in addition, TGF-β1concentration in supernatant of co-culture Tcells was259.25±32.78pg/ml, it was more than blank group202.75±20.17pg/ml. B7-H4had no significant effect on apoptosis of T cells.Conclusion: B7-H4aberrantly expresses in human cervical cancers,and it is associates with decreasing tumor-infiltrating CD8~+T lymphocytes and their IFN-γ secretion. B7-H4plays role on depressing anti-tumor T cellimmune response in the microenvironment of cervical cancers. B7-H4arrested cervical cancer patients’ peripheral blood T cells in G2phase anddecrease the S phase cells; B7-H4inhibits the proliferation of CD4~+T andCD8~+T, but has no significant role on the proliferation of Tregs and theirTGF-β1secretion. B7-H4has no significant effect on T cells apoptosis.