摘要
目的探讨黑色素瘤细胞鲨烯环氧合酶(SQLE)基因敲除调控肿瘤微环境T细胞浸润影响机体抗肿瘤效应的作用及其分子机制。方法使用SQLE敲除的B16F10细胞系分别接种免疫完全和免疫缺陷小鼠,明确基因敲除对肿瘤细胞恶性表型的自主和非自主性调控,进一步使用抗体阻断、Luminex多因子检测和流式细胞等技术探索SQLE基因敲除对细胞因子/趋化因子分泌及免疫浸润的影响,结合生物信息学分析,验证SQLE表达与免疫浸润和临床预后的相关性。结果与免疫缺陷型小鼠相比,敲除SQLE显著抑制免疫完全小鼠肿瘤增殖,延长小鼠生存期。SQLE敲除诱导肿瘤细胞分泌细胞因子和趋化因子,增加肿瘤微环境CD8+T细胞浸润从而改善机体抗肿瘤效应。生物信息学分析提示SQLE及其对应的免疫浸润标志物与黑色素瘤患者临床预后明显相关。结论SQLE通过细胞因子和趋化因子调控肿瘤微环境参与机体抗肿瘤效应,有望成为新的肿瘤免疫药物靶点和疗效预测分子指标。
Objective To investigate the role of squalene epoxidase(SQLE)knockout in anti-tumor effect vial improving CD8+T cell infiltration in melanoma tumor microenvironment.Methods Both immunodeficient and immunocompetent mice were inoculated with SQLE knockout B16F10 cells to determine the cell-autonomous and non-autonomous regulation of malignancy.Antibody blockade,Luminex multiplex assays,and flow cytometry were employed to explore the impact of SQLE gene knockout on the secretion of cytokines/chemokines and immune cell infiltration.Bioinformatics analysis was conducted to validate the correlation between SQLE expression and immune infiltration as well as clinical prognosis in melanoma patients.Results Compared with immunodeficient mice,SQLE knockout significantly inhibited melanoma proliferation in immunocompetent mice and prolonged their survival.SQLE knockout induced the secretion of cytokines and chemokines from tumor cells,improved CD8+T cell infiltration in the tumor microenvironment,thereby potentiating anti-tumor immunity.Bioinformatics analysis suggested a significant correlation between SQLE and its corresponding immune infiltration markers with the prognosis of melanoma patients.Conclusion SQLE regulates anti-tumor immunity by controlling cytokines and chemokines releasing in tumor microenvironment,thus holding promise as a novel tumor immunotherapy target and efficacy prediction molecular indicator.
作者
丁瑶
刘雯
廖亦然
雷舜
张妍
陈叶梓
龚奕
黄启钊
Ding Yao;Liu Wen;Liao Yiran;Lei Shun;Zhang Yan;Chen Yezi;Gong Yi;Huang Qizhao(Dept of Phase I Clinical Trial Ward,Chongqing University Cancer Hospital,Chongqing 400030;Institute of Immunological Innovation and Translation,Chongqing Medical University,Chongqing 400016;Institute of Immunology,Third Military Medical University,Chongqing 400038)
出处
《安徽医科大学学报》
CAS
北大核心
2024年第8期1315-1322,共8页
Acta Universitatis Medicinalis Anhui
基金
重庆市自然科学基金创新发展联合基金重点项目(编号:CSTB2023NSCQ-LZX0010)
国家自然科学基金(编号:81702443)。
