复发转移性头颈鳞状细胞癌免疫治疗现状和探索

目的 世界范围内,头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)发病率在恶性肿瘤中居第7位,复发转移性(recurrent or metastatic,R/M) HNSCC生活质量下降,治疗方法少,预后差.近年来,以免疫检查点抑制剂为代表的免疫治疗取得突破性进展,成为黑色素瘤、肺癌等多种肿瘤有效的治疗选择.本研究对R/M HNSCC免疫治疗的现状和进展作一综述.方法 以“头颈鳞癌,免疫治疗,免疫检查点抑制剂,过继T细胞治疗,肿瘤疫苗”等为关键词,应用PubMed和CNKI期刊全文数据库检索系统以及ClinicalTrials.gov网站,检索2001-01-2017-01的相关文献及注册临床研究,共检索到英文文献138篇,中文文献84篇.纳入标准:(1)R/M HNSCC;(2)免疫治疗现状及进展;(3)免疫治疗相关临床研究.共纳入38篇文献进行分析.结果 R/M HNSCC中免疫治疗研究广泛开展并逐渐深入,尤其是免疫检查点抑制剂.程序性细胞死亡1(programmed cell death-1,PDq)抑制剂(Pembrolizumab和Nivolumab)显示出明显疗效,因此被食品药品管理局(food and drug administration,FDA)批准用于R/M HNSCC的治疗.尽管其他免疫检查点抑制剂如程序性死亡配体1(programmed death ligand-1,PD-L1)抑制剂(Durvalumab和Avelumab)和细胞毒T淋巴细胞相关抗原4(cytotoxic T lymphocyte-associated antigen-4,CTLA-4)抑制剂(Ipilimumab和Tremelimumab)尚无Ⅲ期临床研究结果发表来证明其确切疗效,但有一系列临床研究正在进行中.过继T细胞治疗和肿瘤疫苗的免疫治疗模式也在探索中.此外,在R/M HNSCC免疫治疗中根据生物标志物筛选有效患者,联合治疗提高疗效以及不良反应的监测及治疗等方面也被关注.结论 R/M HNSCC中免疫治疗有良好前景,但也存在许多挑战,如何筛选免疫治疗最有效的人群、探索免疫治疗模式及提高疗效仍是未来研究重点.

Immunotherapy in recurrent or metastatic head and neck squamous cell carcinoma: current status and future explorations

OBJECTIVE Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer worldwide.Recurrent or metastatic (R/M) HNSCC have rare treatment methods with poor prognosis.Recently,immunotherapy,especially immune checkpoint inhibitors,has make great breakthrough in solid tumors such as melanoma and lung cancer.This review was to summarize the current status and perspectives of immunotherapy in R/M HNSCC.METHODS Two hundred and twenty-two related papers and clinical trails were searched with "head and neck squamous cell carcinoma,immunotherapy,immune checkpoint inhibitors,adoptive cell transfer,tumor vaccine" as key words within PubMed or CNKI database retrieval system and ClinicalTrials.gov website from January 2001 to January 2017,and 38 were finally selected according to the inclusion criteria as follows:(1) R/M HNSCC；(2) current status and future perspective of immunotherapy;(3) immunotherapy related clinical trials.RESULTS Researches of immunotherapy in R/M HNSCC immunotherapy have developed wildly and deepened gradually,especially immune checkpoint inhibitors.Programmed cell death-1(PD-1) inhibitors (pembrolizumab and nivolumab) showed obvious effect,and were approved by food and drug administration (FDA) for the treatment of R/M HNSCC.Although there are no results of phase 3 clinical trials related to other immune checkpoint inhibitors,such as programmed death ligand-1 (PD-L1) inhibitors (durvalumab and avelumab) and Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) inhibitors (ipilimumab and tremelimumab)published,a series of clinical trials are ongoing.The modes of adoptive cell transfer and tumor vaccine are explored.Besides,many aspects of immunotherapy in R/M HNSCC,such as screening patients according to biomarkers,improving efficacy with combination methods,monitoring and treatment of adverse events also catch our attentions.CONCLUSIONS Immunotherapy has a bright prospect in R/M HNSCC,but there are also many challenges.Future studies should focus on how to screen the most effective population,explore immune treatment modes and improve the efficacy of immunotherapy.