Neoantigen-targeted CD8+ T cell responses with PD-1 blockade therapy

CD8型 免疫疗法 T细胞受体 T细胞 免疫学 细胞毒性T细胞 生物 人类白细胞抗原 黑色素瘤 抗原 癌症研究 免疫系统 遗传学 体外
作者
Cristina Puig-Saus,Barbara Sennino,Songming Peng,Clifford L. Wang,Zheng Pan,Benjamin Yuen,Bhamini Purandare,Duo An,Boi Quach,Diana Nguyen,Huiming Xia,Sameeha Jilani,Kevin Shao,Claire McHugh,John P. Greer,Phillip Peabody,Saparya Nayak,Jonathan Hoover,Sara Said,Kyle Jacoby
出处
期刊:Nature [Nature Portfolio]
卷期号:615 (7953): 697-704 被引量:110
标识
DOI:10.1038/s41586-023-05787-1
摘要

Neoantigens are peptides derived from non-synonymous mutations presented by human leukocyte antigens (HLAs), which are recognized by antitumour T cells1-14. The large HLA allele diversity and limiting clinical samples have restricted the study of the landscape of neoantigen-targeted T cell responses in patients over their treatment course. Here we applied recently developed technologies15-17 to capture neoantigen-specific T cells from blood and tumours from patients with metastatic melanoma with or without response to anti-programmed death receptor 1 (PD-1) immunotherapy. We generated personalized libraries of neoantigen-HLA capture reagents to single-cell isolate the T cells and clone their T cell receptors (neoTCRs). Multiple T cells with different neoTCR sequences (T cell clonotypes) recognized a limited number of mutations in samples from seven patients with long-lasting clinical responses. These neoTCR clonotypes were recurrently detected over time in the blood and tumour. Samples from four patients with no response to anti-PD-1 also demonstrated neoantigen-specific T cell responses in the blood and tumour to a restricted number of mutations with lower TCR polyclonality and were not recurrently detected in sequential samples. Reconstitution of the neoTCRs in donor T cells using non-viral CRISPR-Cas9 gene editing demonstrated specific recognition and cytotoxicity to patient-matched melanoma cell lines. Thus, effective anti-PD-1 immunotherapy is associated with the presence of polyclonal CD8+ T cells in the tumour and blood specific for a limited number of immunodominant mutations, which are recurrently recognized over time.
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
PDF的下载单位、IP信息已删除 (2025-6-4)

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
zys发布了新的文献求助30
刚刚
grace发布了新的文献求助10
1秒前
kkk发布了新的文献求助10
2秒前
英姑应助老迟到的沛萍采纳,获得10
2秒前
aaaaaa完成签到,获得积分10
2秒前
Janson完成签到,获得积分10
3秒前
ding应助英勇的人生采纳,获得10
4秒前
Orange应助哈哈采纳,获得10
5秒前
Nathan完成签到,获得积分10
5秒前
小菜完成签到,获得积分20
5秒前
Carrot发布了新的文献求助10
6秒前
6秒前
温冰雪完成签到,获得积分10
8秒前
nanfeng完成签到,获得积分10
10秒前
10秒前
waayu完成签到 ,获得积分10
11秒前
迷人芙蓉发布了新的文献求助10
12秒前
量子星尘发布了新的文献求助10
12秒前
搜集达人应助kassidy采纳,获得10
13秒前
13秒前
罗那完成签到,获得积分10
13秒前
14秒前
vv关闭了vv文献求助
15秒前
科研通AI2S应助研友_RLNXOZ采纳,获得10
15秒前
852应助Whale采纳,获得10
15秒前
16秒前
王者归来发布了新的文献求助30
16秒前
17秒前
猪猪hero应助鲤鱼安青采纳,获得10
17秒前
失眠水风完成签到,获得积分10
17秒前
17秒前
Rondab应助shinn采纳,获得10
18秒前
westbobo发布了新的文献求助10
18秒前
19秒前
20秒前
21秒前
啊啊啊发布了新的文献求助10
23秒前
科目三应助westbobo采纳,获得10
23秒前
23秒前
24秒前
高分求助中
Picture Books with Same-sex Parented Families: Unintentional Censorship 700
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
Effective Learning and Mental Wellbeing 300
热门求助领域 (近24小时)
化学 材料科学 医学 生物 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 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3975339
求助须知:如何正确求助?哪些是违规求助? 3519670
关于积分的说明 11199199
捐赠科研通 3256002
什么是DOI,文献DOI怎么找? 1798043
邀请新用户注册赠送积分活动 877386
科研通“疑难数据库(出版商)”最低求助积分说明 806305