Cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) tumour expression in gastric carcinoma

Background & objectives Immune checkpoint inhibitor (ICI) therapy is an emerging therapeutic strategy for several malignancies, including gastric cancer, that hinges on immune checkpoint expression by the tumour infiltrating lymphocytes (TILs). Cytotoxic T lymphocyte associated antigen-4 (CTLA-4) is a well-known inhibitory T-cell co-receptor that functions as an immune checkpoint. CTLA-4 has also been found to be expressed by tumour cells making it a potential area of research for targeted therapy. We attempted to explore tumour cell CTLA-4 expression, and its correlation with programmed cell death receptor-1 (PD-1) and CD8 expression by the TILs and their correlations with histopathological parameters in gastric carcinoma. Methods A retrospective study carried out on archived paraffin blocks from 50 cases of gastric adenocarcinoma. Immunohistochemical (IHC) staining was performed and interpreted by grading the marker expression on the basis of its intensity and proportion of tumour cells stained. The relationship between tumour cell CTLA-4 expression, PD-1, CD8 expression in TILs and the histopathological features of gastric carcinoma was evaluated statistically. Results Most patients (n=37, 74%) were males and aged >60 yr (n=22, 44%). A statistically significant association was noted between high CTLA-4 expression in tumour cells and higher tumour stage (P=0.017). All cases with high CTLA-4 expression in tumour cells demonstrated nodal metastasis. CTLA-4 did not show a statistically meaningful association with other histopathological parameters. Positive PD-1 expression in TILs did not show a significant association with tumour aggression in terms of tumour grade, histologic type, nodal metastasis, lymphovascular and perineural invasion. Most TILs were found to be CD8+ T-cells. Interpretation & conclusions A higher CTLA-4 expression in tumour cells is linked to advanced tumour stage in our study. These findings can trigger research to elucidate a likely role of these markers as independent prognostic and therapeutic factors in determining overall outcome in gastric carcinoma.