已入深夜,您辛苦了!由于当前在线用户较少,发布求助请尽量完整的填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!祝你早点完成任务,早点休息,好梦!

Human Leukocyte Antigen Class I Antigen-Processing Machinery Upregulation by Anticancer Therapies in the Era of Checkpoint Inhibitors

医学 免疫学 癌症研究 细胞毒性T细胞 表观遗传学 抗原 抗原处理 癌症 抗原呈递 人类白细胞抗原 免疫系统 T细胞 生物 内科学 基因 体外 生物化学
作者
Ananthan Sadagopan,Theodoros Michelakos,Gabriella Boyiadzis,Cristina R. Ferrone,Soldano Ferrone
出处
期刊:JAMA Oncology [American Medical Association]
卷期号:8 (3): 462-462 被引量:27
标识
DOI:10.1001/jamaoncol.2021.5970
摘要

Importance

Although typically impressive, objective responses to immune checkpoint inhibitors (ICIs) occur in only 12.5% of patients with advanced cancer. The majority of patients do not respond due to cell-intrinsic resistance mechanisms, including human leukocyte antigen (HLA) class I antigen-processing machinery (APM) defects. The APM defects, which have a negative effect on neoantigen presentation to cytotoxic T lymphocytes (CTLs), are present in the majority of malignant tumors. These defects are caused by gene variations in less than 25% of cases and by dysregulated signaling and/or epigenetic changes in most of the remaining cases, making them frequently correctable. This narrative review summarizes the growing clinical evidence that chemotherapy, targeted therapies, and, to a lesser extent, radiotherapy can correct HLA class I APM defects in cancer cells and improve responses to ICIs.

Observations

Most chemotherapeutics enhance HLA class I APM component expression and function in cancer cells, tumor CTL infiltration, and responses to ICIs in preclinical and clinical models. Despite preclinical evidence, radiotherapy does not appear to upregulate HLA class I expression in patients and does not enhance the efficacy of ICIs in clinical settings. The latter findings underscore the need to optimize the dose and schedule of radiation and timing of ICI administration to maximize their immunogenic synergy. By increasing DNA and chromatin accessibility, epigenetic agents (histone deacetylase inhibitors, DNA methyltransferase inhibitors, andEZH2inhibitors) enhance HLA class I APM component expression and function in many cancer types, a crucial contributor to their synergy with ICIs in patients. Furthermore, epidermal growth factor receptor (EGFR) inhibitors and BRAF/mitogen-activated protein kinase kinase inhibitors are effective at upregulating HLA class I expression inEGFR- andBRAF-variant tumors, respectively; these changes may contribute to the clinical responses induced by these inhibitors in combination with ICIs.

Conclusions and Relevance

This narrative review summarizes evidence indicating that chemotherapy and targeted therapies are effective at enhancing HLA class I APM component expression and function in cancer cells. The resulting increased immunogenicity and recognition and elimination of cancer cells by cognate CTLs contributes to the antitumor activity of these therapies as well as to their synergy with ICIs.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
风的忧伤完成签到,获得积分10
1秒前
标致的电灯胆完成签到,获得积分10
5秒前
泠风来完成签到,获得积分10
6秒前
leopardymk发布了新的文献求助10
7秒前
11秒前
11秒前
ZCLLLLL发布了新的文献求助10
12秒前
高贵的雅寒完成签到,获得积分20
16秒前
16秒前
Osiris发布了新的文献求助10
18秒前
孤巷的猫完成签到,获得积分10
20秒前
YBY完成签到 ,获得积分10
20秒前
包容新蕾发布了新的文献求助10
21秒前
21秒前
25秒前
kyfbrahha完成签到 ,获得积分10
26秒前
拼搏的似狮完成签到,获得积分10
27秒前
着急的语海完成签到,获得积分10
29秒前
于清绝完成签到 ,获得积分10
30秒前
qianchimo完成签到 ,获得积分10
37秒前
xiemeili完成签到 ,获得积分10
38秒前
Osiris完成签到,获得积分10
39秒前
40秒前
41秒前
Diligency完成签到 ,获得积分10
41秒前
46秒前
飞翔的霸天哥应助emm采纳,获得30
46秒前
houfei发布了新的文献求助10
47秒前
50秒前
51秒前
chenyuns发布了新的文献求助20
51秒前
冰西瓜完成签到 ,获得积分10
58秒前
尘尘完成签到,获得积分10
1分钟前
似水流年完成签到 ,获得积分10
1分钟前
jhlz5879完成签到 ,获得积分10
1分钟前
Jessie发布了新的文献求助30
1分钟前
chenyuns发布了新的文献求助10
1分钟前
krajicek完成签到,获得积分10
1分钟前
棉袄完成签到 ,获得积分10
1分钟前
aiiLuX完成签到 ,获得积分10
1分钟前
高分求助中
The ACS Guide to Scholarly Communication 2500
Sustainability in Tides Chemistry 2000
Pharmacogenomics: Applications to Patient Care, Third Edition 1000
Studien zur Ideengeschichte der Gesetzgebung 1000
TM 5-855-1(Fundamentals of protective design for conventional weapons) 1000
Threaded Harmony: A Sustainable Approach to Fashion 810
《粉体与多孔固体材料的吸附原理、方法及应用》(需要中文翻译版,化学工业出版社,陈建,周力,王奋英等译) 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3085205
求助须知:如何正确求助?哪些是违规求助? 2738111
关于积分的说明 7548402
捐赠科研通 2387728
什么是DOI,文献DOI怎么找? 1266084
科研通“疑难数据库(出版商)”最低求助积分说明 613281
版权声明 598492