title: Aberrant expression of B7-H4 correlates with poor prognosis and suppresses tumor-infiltration of CD8+ T lymphocytes in human cholangiocarcinoma.
abstract: B7-H4, as a member of the costimulatory B7 family, serves a critical role in the negative regulation of T cell-mediated antitumor immune responses. Cholangiocarcinoma (CCA) has a poor prognosis due its invasiveness and associated metastasis. The present study investigated the expression of B7-H4 in patients with CCA and its association with patient prognosis. The correlation between B7-H4 expression and CD4+ and CD8+ tumor-infiltrating lymphocytes was also investigated. The results demonstrated that high B7-H4 expression was detected in cancer tissues (54/110; 49.1%) compared with that noted in chronic inflammatory bile duct tissues (4/19; 21.1%). Furthermore, all 8 biliary adenoma samples showed negative staining. The expression of B7-H4 was significantly associated with adverse clinical and pathological features including histologic grade (P<0.001), tumor status (P=0.025), lymph node metastasis (P=0.035) and 6th Union for International Cancer Control stage (P=0.019). Kaplan‑Meier survival analysis and Cox regression analysis indicated that aberrant B7-H4 expression was a significant independent predictor of poor overall survival and early recurrence. In addition, the present study demonstrated that B7-H4 expression in tumor cells was negatively correlated with the density of CD8+ T cells in the tumor stroma. Co-culture assays indicated that knockdown of B7-H4 increased CD8+ T cell-mediated cytotoxicity in vitro, suggesting that the expression of B7-H4 may serve a role in shielding tumors from immune surveillance by suppression of tumor-infiltrating CD8+ T lymphocytes in CCA. In conclusion, the present study showed that aberrant expression of B7-H4 was correlated with poorer prognosis and suppressed CD8+ tumor‑infiltrating lymphocytes in CCA.
authors.affiliation: Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Shapingba, Chongqing 400038, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Shapingba, Chongqing 400038, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Guo
authors.affiliation: Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Shapingba, Chongqing 400038, P.R. China.
authors.forename: Zhonghu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Shapingba, Chongqing 400038, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Jiang
authors.affiliation: Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Shapingba, Chongqing 400038, P.R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Deng
authors.affiliation: Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Shapingba, Chongqing 400038, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Tian
authors.affiliation: Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Shapingba, Chongqing 400038, P.R. China.
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Shapingba, Chongqing 400038, P.R. China.
authors.forename: Shuguang
authors.initials: S
authors.lastname: Wang
mesh_terms: D001650:Bile Duct Neoplasms / Q000378:metabolism* / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000473:pathology*; D018920:Coculture Techniques / Q000379:methods; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods; D011379:Prognosis; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1 / Q000378:metabolism*
chemical_list: D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475826:VTCN1 protein, human