title: B7-H1 and B7-H4 expression in colorectal carcinoma: correlation with tumor FOXP3(+) regulatory T-cell infiltration.
abstract: B7-H1 and B7-H4 are newly discovered members of the B7-CD28 family. They can inhibit T cell activation and proliferation and regulate T cell immune response negatively. Both B7-H1 and B7-H4 are expressed in many tumors and are classified as co-inhibitors of cell-mediated immunity. FOXP3(+) regulatory T cells (Tregs) play an important role in the maintenance of tumor immunity tolerance. However, the implication of B7-H1 and B7-H4 expression and their interaction with Tregs infiltration in colorectal cancer are unknown. The present study aimed to determine the expression of B7-H1 and B7-H4 as well as Tregs infiltration in colorectal cancer and to explore the clinical and pathological implication of suppressor immune cells and molecules. Frozen sections and immunohistochemical assay were undertaken to assess B7-H1, B7-H4 expression and Tregs infiltration in fresh specimens collected from 56 patients with colorectal carcinoma. The results showed that expression of B7-H1 and B7-H4 in colorectal carcinoma tissues was significantly higher than in adjacent normal mucosa (P<0.001). B7-H1 expression was positively correlated to the infiltration depth, lymph node metastasis and advanced Duke's stage (P<0.05, P<0.05 and P<0.05, respectively), whereas B7-H4 expression was positively related to the infiltration depth and lymph node metastasis (P<0.01 and P<0.05, respectively). Furthermore, Tregs infiltration was more frequent in tumor tissue than in adjacent normal mucosa and was associated with poor differentiation and positive lymph node metastasis (P<0.01, and P<0.01, respectively). The statistical analysis indicated a significant correlation between Tregs infiltration and B7-H1 or B7-H4 expression respectively. These results suggest that over-expression of B7-H1 and B7-H4 has stronger prognostic significance and promote tumor tolerance, and they might contribute to Tregs development in the colorectal carcinoma tolerogenic milieu.
authors: Department of Pathology, School of Basic Medical Sciences, Beihua University, Jilin, Jilin 132013, People's Republic of China; Department of Pathology, School of Basic Medical Sciences, Jilin Medical College, Jilin, Jilin 132013, People's Republic of China.
authors: Li-wei
authors: LW
authors: Zhao
authors: Department of Pathology, School of Basic Medical Sciences, Beihua University, Jilin, Jilin 132013, People's Republic of China.
authors: Chun
authors: C
authors: Li
authors: Department of Pathology, School of Basic Medical Sciences, Beihua University, Jilin, Jilin 132013, People's Republic of China.
authors: Rui-lan
authors: RL
authors: Zhang
authors: Department of Surgery, Affiliated Hospital of Beihua University, Jilin, Jilin 132013, People's Republic of China.
authors: Hao-gang
authors: HG
authors: Xue
authors: Department of Surgery, Affiliated Hospital of Beihua University, Jilin, Jilin 132013, People's Republic of China.
authors: Fu-xi
authors: FX
authors: Zhang
authors: Department of Pathology, School of Basic Medical Sciences, Beihua University, Jilin, Jilin 132013, People's Republic of China.
authors: Fan
authors: F
authors: Zhang
authors: Department of Pathology, School of Basic Medical Sciences, Beihua University, Jilin, Jilin 132013, People's Republic of China. Electronic address: bhdxgaixiaodong@126.com.
authors: Xiao-dong
authors: XD
authors: Gai
mesh_terms: D000328:Adult; D000368:Aged; D060890:B7-H1 Antigen / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D019139:Tumor Escape; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1 / Q000378:metabolism*
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475826:VTCN1 protein, human
keywords: B7-H1; B7-H4; Colorectal cancer; Immunohistochemistry; Regulatory T cells