关键词: Vδ1 γδ T细胞, F-Box蛋白2(FBXO2), 异位蛋白质, 肿瘤免疫治疗靶点

Abstract: Objective To validate F-box protein 2 (FBXO2) as a potential tumor-specific pattern recognition ligand for γδ T cells and to characterize its expression in tumor cells and function in immunotherapy. Methods The expression of FBXO2 in various human solid tumor and hematological tumor cell lines was detected by Western blot and flow cytometry. Immobilized FBXO2 recombinant protein was used to expand Vδ2 and Vδ1 γδ T cells from human peripheral blood mono-nuclear cell(PBMC), followed by comprehensive characterization of cellular purity, absolute counts, activation marker expression and cytokine secretion profiles. The inhibitory effect of FBXO2-specific antibody on the in vitro cytotoxicity of Vδ1and Vδ2 γδ T cells was evaluated via antibody blockade experiment. Results FBXO2 was expressed in some human solid and hematological tumor cell lines especially in the gastric cancer line SNU601 and the lymphocyte leukemia line Jurkat. Immobilized FBXO2 significantly promoted the expansion of Vδ1 γδ T cells but failed to stimulate Vδ2 γδ T cells. Vδ1 γδ T cells exerted cytotoxic activity by recognizing FBXO2 protein while FBXO2 antibody blocked their cytotoxic effects on SNU601 and Jurkat cells with a dose-dependent manner in vitro. Conclusions F-Box2 protein, ectopically expressed on a variety of tumor cell surface, may promote the expansion of Vδ1 γδ T cells and enhance the cytotoxicity of γδ T cells against tumor cells in vitro,so this protein molecule is believed to be a tumor-associated protein ligand recognized by γδ T cells. This result suggests a potential nascent target for cancer immunotherapy.

Key words: Vδ1 γδ T cell, F-box only protein 2(FBXO2), ectopic protein, tumor immunotherapy target