免疫检查点及其抑制剂在口腔鳞状细胞癌治疗中的进展

Advances in immune checkpoints and their inhibitors in oral squamous cell carcinoma therapy

目的本研究旨在为口腔鳞状细胞癌(OSCC)免疫治疗方案的改进和完善提供思路。方法采用PubMed、Web of Science、中国知网全文数据库检索系统,以中文"口腔鳞状细胞癌、免疫检查点、免疫检查点抑制剂"和英文"oral squamous cell carcinoma、immune checkpoints、immune checkpoint inhibitors"为检索词,检索2015-01-01-2020-01-31相关文献,共341篇英文文献和26篇中文文献。纳入标准:(1)OSCC发生、发展及预后过程中免疫检查点(ICs)的表达分析;(2)免疫检查点抑制剂(ICIs)在OSCC中的运用;(3)ICIs在肿瘤治疗中引起的毒副作用及其应对策略。排除标准:通过文献摘要阅读,凡不符合纳入标准的文献均排除。根据纳入和排除标准,对36篇文献进行分类、总结和分析,并对OSCC免疫治疗的未来进行了展望。结果ICs在OSCC中通常高表达且受其他蛋白调控,其受体在肿瘤免疫微环境中的表达也会发生改变。ICs基因在不同状态的OSCC中对预后的影响具有差异,且ICs调节分子对OSCC的预后也有影响。部分ICIs在OSCC中产生疗效,但其治疗效果还跟RNA编辑酶功能、肿瘤相关较弱的炎症反应、调节性T细胞(Treg)、干扰素的双重作用等具有重要联系,可参考联合策略来增强疗效。ICIs疗法虽取得了较好疗效,但是毒副作用不容忽视,"关闭策略"可能在抑制免疫相关不良事件上具有一定效果。结论ICs的异常表达关系到OSCC的发生、发展和预后,ICIs治疗对OSCC有利有弊,未来需进行加强疗效减少毒副作用的研究。

Objective To provide clues for the improvement of OSCC immunotherapy.Methods Keywords such as"oral squamous cell carcinoma,immune checkpoints and immune checkpoint inhibitors"were used to retrieve related references from January 1,2015 to January 31,2020 in PubMed,Web of Science and China National Knowledge infrastructure,including 341 English references and 26 Chinese references.Inclusion criteria:(1)The analysis of the expression of ICs during the occurrence,development and prognosis of OSCC;(2)Using of ICIs in OSCC;(3)The side effects of ICIs in tumor treatment and their coping strategies.Exclusion criteria:Through reading the abstract of these references,any reference that didn’t meet the inclusion criteria was excluded.According to the inclusion and exclusion criteria,36 references were classified,summarized and analyzed,and the future of OSCC immunotherapy was prospected.Results ICs are usually highly expressed in OSCC and regulated by other proteins,and the expression of their receptors in the tumor immune microenvironment will also be changed;ICs genes have different effects on prognosis in different states of OSCC,and their regulators also have effects on the prognosis of OSCC;some ICIs have therapeutic effects in OSCC,but their therapeutic effects are also importantly related to the function of RNA editing enzymes,weak tumor-related inflammatory responses,the dual role of interferon and Treg cells,and will be enhanced by some combined strategies;ICIs therapy have achieved good results,but the side effects can not be ignored,and the"shutdown strategy"may have a certain effect in suppressing immune-related adverse events.Conclusions The abnormal expression of ICs is related to the occurrence,development and prognosis of OSCC.ICIs have advantages and disadvantages in the treatment of OSCC.In the future,it will be necessary to strengthen the research on the efficacy and reduction of the side effects.