Expression of TIGIT/CD155 and correlations with clinical pathological features in human hepatocellular carcinoma

摘要

T cell immunoglobulin and ITIM domain (TIGIT) is a recently identified T cell coinhibitory receptor. Studies have shown that TIGIT is expressed in colon adenocarcinoma, uterine corpus endometrioid carcinoma, breast carcinoma and kidney renal clear cell carcinoma. However, the role of the TIGIT/human poliovirus receptor (CD155) pathway in the pathogenesis of hepatocellular carcinoma (HCC) remains to be elucidated. In the present study, the expression of TIGIT and CD155 in HCC tissues and peripheral blood were determined, and correlations among TIGIT, CD155, TIGIT⁺ CD4⁺ T cells, TIGIT⁺ regulatory T (Treg) cells and α-fetoprotein (AFP) were investigated in order to identify a potential target for diagnosing and treating HCC. Immunohistochemistry, reverse transcription-quantitative PCR analysis and western blotting were used to examine the expression of TIGIT and CD155 in cancerous tissues and peripheral blood collected from patients with HCC. The frequency of TIGIT⁺ CD4⁺ T cells and TIGIT⁺ Treg cells and the concentration of inflammatory cytokines secreted by T cell subsets were analyzed by flow cytometry and a Merck Milliplex assay. Correlations between the frequency of TIGIT⁺ CD4⁺ T and TIGIT⁺ Treg cells and AFP were analyzed using Spearman's rank correlation test. With the degree of cancerous differentiation from high to low, the expression levels of TIGIT and CD155 were upregulated in the cancerous tissues from patients with HCC. TIGIT⁺ CD4⁺ T cell and TIGIT⁺ Treg cell frequencies were decreased in peripheral blood from postoperative patients with HCC. The increased expression of TIGIT was positively correlated with the level of AFP. These results indicate that co-inhibitory receptor TIGIT may be involved in the pathogenesis of HCC and represent a novel target for the diagnosis and treatment of HCC.