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浙江大学学报（医学版）
浙江大学学报（医学版）  2021, Vol. 50 Issue (6): 675-684    DOI: 10.3724/zdxbyxb-2021-0273
专题报道     
甲状腺未分化癌免疫治疗的现状及未来
卢茜璇1,2,包黎莎1,2,潘宗富2,3,*(),葛明华1,2,*()
1.杭州医学院附属人民医院 浙江省人民医院耳鼻喉科-头颈外科中心头颈外科，浙江杭州 310014
2.浙江省内分泌腺体疾病诊治研究重点实验室，浙江 杭州 310014
3.杭州医学院附属人民医院 浙江省人民医院临床药学中心药学部，浙江 杭州 310014
Immunotherapy for anaplastic thyroid carcinoma: the present and future
LU Xixuan1,2,BAO Lisha1,2,PAN Zongfu2,3,*(),GE Minghua1,2,*()
1. Department of Head and Neck Surgery, Center of Otolaryngology, Head and Neck Surgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou 310014, China;
2. Zhejiang Provincial Key Laboratory of Endocrine Gland Diseases, Hangzhou 310014, China;
3. Department of Pharmacy, Clinical Pharmacy Center, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou 310014, China
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摘要：

甲状腺未分化癌（ATC）是恶性程度最高的内分泌系统肿瘤，是当前亟待攻克的医学难题。目前，针对ATC的免疫治疗研究主要包括阻断肿瘤相关巨噬细胞（TAM）的招募、诱导TAM重编程以及恢复其吞噬功能；靶向T淋巴细胞及自然杀伤细胞的相关免疫逃逸检查点；基于溶瘤病毒和树突状细胞的肿瘤疫苗以及过继免疫治疗。其中，以靶向阻断免疫检查点程序性死亡蛋白1/程序性死亡蛋白配体1为代表的免疫治疗策略已初步证实对ATC患者有获益，尤其是分子靶向抑制剂联合免疫治疗具有极佳的治疗效果。由于ATC存在极大的异质性，针对ATC开展包括生物、免疫或细胞治疗等多种免疫治疗研究，并探索下一代免疫检查点抑制剂对ATC的治疗潜力，有望为ATC患者提供更丰富的治疗策略。本文综述了ATC的免疫治疗潜在靶点以及相关的免疫疗法进展。
关键词： 甲状腺未分化癌;  免疫逃逸;  临床研究;  免疫治疗;  综述    
Abstract:

Anaplastic thyroid carcinoma (ATC) is the most malignant tumor of endocrine system, which is an urgent medical problem to be solved. At present, immunotherapy studies on ATC mainly include cutting off the recruitment of tumor-associated macrophage (TAM), inducing the reprogramming of TAM and restoring its phagocytic function, targeting related immune checkpoints on T cells and natural killer cells, tumor vaccines based on oncolytic viruses and dendritic cells, and adoptive immunotherapy. Among them, immunotherapy strategies represented by targeted blocking of programmed death-1/programmed death ligand-1 at immune checkpoint have been preliminarily confirmed to benefit ATC patients, especially the combination of molecular targeted inhibitors and immunotherapy has shown excellent therapeutic effects. Due to the great heterogeneity of ATC, it is expected to provide more therapeutic strategies for patients of ATC by carrying out various immunotherapy studies including biological, immune and cellular therapies and exploring the therapeutic potential of the next generation of immune checkpoint inhibitors. This article reviews the potential immunotherapeutic targets of ATC and the progress of immunotherapy.
Key words: Anaplastic thyroid carcinoma    Immune escape    Clinical study    Immunotherapy    Review
收稿日期: 2021-08-10 出版日期: 2022-03-22
CLC:  R736.1  
基金资助: 国家自然科学基金（U20A20382，81872170，82173157，81802673）；浙江省医药卫生科技计划（2021KY056）
通讯作者: 潘宗富,葛明华     E-mail: geminghua@hmc.edu.cn
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引用本文:

卢茜璇,包黎莎,潘宗富,葛明华. 甲状腺未分化癌免疫治疗的现状及未来[J]. 浙江大学学报（医学版）, 2021, 50(6): 675-684.

LU Xixuan,BAO Lisha,PAN Zongfu,GE Minghua. Immunotherapy for anaplastic thyroid carcinoma: the present and future. J Zhejiang Univ (Med Sci), 2021, 50(6): 675-684.

链接本文:

https://www.zjujournals.com/med/CN/10.3724/zdxbyxb-2021-0273    或    https://www.zjujournals.com/med/CN/Y2021/V50/I6/675

图 1  甲状腺未分化癌免疫治疗潜在靶点及干预策略ATC细胞通过重塑肿瘤免疫微环境逃避免疫监视，目前的干预策略主要包括：①阻断TAM招募、诱导TAM重编码以及恢复TAM肿瘤吞噬能力；②靶向T淋巴细胞及自然杀伤细胞的相关免疫逃逸检查点；③基于溶瘤病毒和树突状细胞的肿瘤疫苗以及以CAR-T为主的过继免疫疗法. ATC：甲状腺未分化癌；TAM：肿瘤相关巨噬细胞；SIRP：信号调节蛋白；CSF：集落刺激因子；CSF-1R：集落刺激因子1受体；CCL：趋化因子CC亚家族配体；CCR：趋化因子CC亚家族受体；CAR-T：嵌合抗原受体T细胞；ULBP：UL16结合蛋白；ICAM：细胞间黏附分子；NKG2D：自然杀伤细胞2族成员D；CXCR：趋化因子CXC亚家族受体；CXCL：趋化因子CXC亚家族配体.
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