FBXO2是Vδ1 γδ T细胞识别的肿瘤相关异位蛋白质配体OA

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 hu-man peripheral blood mono-nuclear cell(PBMC),followed by comprehensive characterization of cellular purity,ab-solute 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 ex-pansion of Vδ1 γδ T cells but failed to stimulate Vδ2 γδ T cells.Vδ1 γδ T cells exerted cytotoxic activity by recog-nizing 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 sur-face,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 re-sult suggests a potential nascent target for cancer immunotherapy.