Multiomics and spatial mapping characterizes human CD8 + T cell states in cancer

生物 癌症 计算生物学 遗传学
作者
Stefan Naulaerts,Angeliki Datsi,Daniel Borràs,Asier Antoranz,Julie Messiaen,Isaure Vanmeerbeek,Jenny Sprooten,Raquel S. Laureano,Jannes Govaerts,Dena Panovska,Marleen Derweduwe,Michael Sabel,Marion Rapp,Weiming Ni,Sean Mackay,Yannick Van Herck,Lendert Gelens,Tom Venken,Sanket More,Oliver Bechter,Gabriele Bergers,Adrian Liston,Steven De Vleeschouwer,Benoı̂t J. Van den Eynde,Diether Lambrechts,Michiel Verfaillie,Francesca Maria Bosisio,Sabine Tejpar,Jannie Borst,Rüdiger V. Sorg,Frederik De Smet,Abhishek D. Garg
出处
期刊:Science Translational Medicine [American Association for the Advancement of Science]
卷期号:15 (691) 被引量:41
标识
DOI:10.1126/scitranslmed.add1016
摘要

Clinically relevant immunological biomarkers that discriminate between diverse hypofunctional states of tumor-associated CD8 + T cells remain disputed. Using multiomics analysis of CD8 + T cell features across multiple patient cohorts and tumor types, we identified tumor niche–dependent exhausted and other types of hypofunctional CD8 + T cell states. CD8 + T cells in “supportive” niches, like melanoma or lung cancer, exhibited features of tumor reactivity–driven exhaustion (CD8 + T EX ). These included a proficient effector memory phenotype, an expanded T cell receptor (TCR) repertoire linked to effector exhaustion signaling, and a cancer-relevant T cell–activating immunopeptidome composed of largely shared cancer antigens or neoantigens. In contrast, “nonsupportive” niches, like glioblastoma, were enriched for features of hypofunctionality distinct from canonical exhaustion. This included immature or insufficiently activated T cell states, high wound healing signatures, nonexpanded TCR repertoires linked to anti-inflammatory signaling, high T cell–recognizable self-epitopes, and an antiproliferative state linked to stress or prodeath responses. In situ spatial mapping of glioblastoma highlighted the prevalence of dysfunctional CD4 + :CD8 + T cell interactions, whereas ex vivo single-cell secretome mapping of glioblastoma CD8 + T cells confirmed negligible effector functionality and a promyeloid, wound healing–like chemokine profile. Within immuno-oncology clinical trials, anti–programmed cell death protein 1 (PD-1) immunotherapy facilitated glioblastoma’s tolerogenic disparities, whereas dendritic cell (DC) vaccines partly corrected them. Accordingly, recipients of a DC vaccine for glioblastoma had high effector memory CD8 + T cells and evidence of antigen-specific immunity. Collectively, we provide an atlas for assessing different CD8 + T cell hypofunctional states in immunogenic versus nonimmunogenic cancers.
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
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
刚刚
大方的半莲完成签到,获得积分10
1秒前
小马甲应助王木木采纳,获得10
1秒前
畅快莹芝完成签到,获得积分10
2秒前
2秒前
2秒前
lufang发布了新的文献求助10
3秒前
无花果应助yuyuyuan采纳,获得10
3秒前
123稻稻人完成签到 ,获得积分10
5秒前
七月发布了新的文献求助10
5秒前
Kathy完成签到,获得积分10
8秒前
jingjing完成签到 ,获得积分10
8秒前
不安溪灵完成签到,获得积分10
11秒前
ann完成签到,获得积分10
13秒前
独特语琴发布了新的文献求助10
13秒前
14秒前
wanci应助七月采纳,获得10
14秒前
123完成签到,获得积分10
14秒前
24秒前
24秒前
彭于晏应助XIXI采纳,获得10
26秒前
orixero应助sue401采纳,获得10
27秒前
xiong完成签到 ,获得积分10
27秒前
小柒柒完成签到,获得积分10
27秒前
杰克李李完成签到,获得积分10
27秒前
27秒前
欢呼的凌兰完成签到,获得积分10
29秒前
123完成签到,获得积分10
30秒前
30秒前
情怀应助独特语琴采纳,获得10
32秒前
研友_O8Wz4Z发布了新的文献求助200
33秒前
darkpigx完成签到,获得积分10
33秒前
香蕉觅云应助自觉紫安采纳,获得10
33秒前
伶俐白凝完成签到 ,获得积分10
36秒前
38秒前
东风徐来完成签到,获得积分10
39秒前
40秒前
40秒前
puheshengwu完成签到,获得积分10
41秒前
41秒前
高分求助中
Les Mantodea de Guyane Insecta, Polyneoptera 2500
Mobilization, center-periphery structures and nation-building 600
Technologies supporting mass customization of apparel: A pilot project 450
China—Art—Modernity: A Critical Introduction to Chinese Visual Expression from the Beginning of the Twentieth Century to the Present Day 430
Tip60 complex regulates eggshell formation and oviposition in the white-backed planthopper, providing effective targets for pest control 400
A Field Guide to the Amphibians and Reptiles of Madagascar - Frank Glaw and Miguel Vences - 3rd Edition 400
China Gadabouts: New Frontiers of Humanitarian Nursing, 1941–51 400
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 物理 生物化学 纳米技术 计算机科学 化学工程 内科学 复合材料 物理化学 电极 遗传学 量子力学 基因 冶金 催化作用
热门帖子
关注 科研通微信公众号,转发送积分 3793333
求助须知:如何正确求助?哪些是违规求助? 3338077
关于积分的说明 10288655
捐赠科研通 3054718
什么是DOI,文献DOI怎么找? 1676139
邀请新用户注册赠送积分活动 804145
科研通“疑难数据库(出版商)”最低求助积分说明 761757