免疫检查点
CD8型
乳腺癌
免疫系统
癌症研究
免疫疗法
三阴性乳腺癌
肿瘤微环境
肿瘤科
癌症
颗粒酶B
医学
颗粒酶
癌细胞
细胞毒性T细胞
生物
内科学
免疫学
穿孔素
体外
生物化学
作者
Xiao Qian Wang,Esther Danenberg,Chiun‐Sheng Huang,Daniel Egle,Maurizio Callari,Begoña Bermejo,Matteo Dugo,Claudio Zamagni,Marc Thill,Anton Anton,Stefania Zambelli,Stefania Russo,Eva Ciruelos,Richard Greil,Balázs Győrffy,Vladimir Semiglazov,Marco Colleoni,Catherine M. Kelly,Gabriella Mariani,Lucia Del Mastro
出处
期刊:Nature
[Nature Portfolio]
日期:2023-09-06
卷期号:621 (7980): 868-876
被引量:255
标识
DOI:10.1038/s41586-023-06498-3
摘要
Abstract Immune checkpoint blockade (ICB) benefits some patients with triple-negative breast cancer, but what distinguishes responders from non-responders is unclear 1 . Because ICB targets cell–cell interactions 2 , we investigated the impact of multicellular spatial organization on response, and explored how ICB remodels the tumour microenvironment. We show that cell phenotype, activation state and spatial location are intimately linked, influence ICB effect and differ in sensitive versus resistant tumours early on-treatment. We used imaging mass cytometry 3 to profile the in situ expression of 43 proteins in tumours from patients in a randomized trial of neoadjuvant ICB, sampled at three timepoints (baseline, n = 243; early on-treatment, n = 207; post-treatment, n = 210). Multivariate modelling showed that the fractions of proliferating CD8 + TCF1 + T cells and MHCII + cancer cells were dominant predictors of response, followed by cancer–immune interactions with B cells and granzyme B + T cells. On-treatment, responsive tumours contained abundant granzyme B + T cells, whereas resistant tumours were characterized by CD15 + cancer cells. Response was best predicted by combining tissue features before and on-treatment, pointing to a role for early biopsies in guiding adaptive therapy. Our findings show that multicellular spatial organization is a major determinant of ICB effect and suggest that its systematic enumeration in situ could help realize precision immuno-oncology.
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