Title | Multiplexed imaging mass cytometry reveals distinct tumor-immune microenvironments linked to immunotherapy responses in melanoma |
Authors | Xu Xiao Qian Guo Chuanliang Cui Yating Lin Lei Zhang Xin Ding Qiyuan Li Minshu Wang Wenxian Yang Yan Kong Rongshan Yu |
Affiliation | Xiamen University Peking University Cancer Hospital and Research Institute Zhongshan Hospital Xiamen University Aginome Scientific |
Keywords | Imaging mass cytometry tumor microenvironment melanoma immunotherapy single-cell imaging |
Issue Date | 22-Mar-2023 |
Publisher | 2022CCTB中国肿瘤标志物学术大会暨中国整合肿瘤学大会暨第十六届肿瘤标志物青年科学家论坛暨中国肿瘤标志物产业创新大会论文集 |
Abstract | Background:Single-cell technologies have enabled extensive analysis of complex immune composition,phenotype and interactions within tumor,which is crucial in understanding the mechanisms behind cancer progression and treatment resistance.Unfortunately,the knowledge on cell phenotypes and their spatial interactions at present has only limited utilization in guiding pathological stratification on patients based on their immune microenvironments for better clinical decisions.Methods:Here we used imaging mass cytometry to simultaneously quantify 35 proteins in a spatially resolved manner on tumor tissues from 26 melanoma patients(14 responders and 12nonresponders) receiving anti-programmed cell death-1(anti-PD-1) therapy.Results:Combined single-cell and spatial analysis reveals highly dynamic tumor microenvironments(TMEs) that are characterized with variable tumor and immune cell phenotypes and their spatial organizations in melanomas,and many of these multicellular features are associated with response to anti-PD-1 therapy.We further identify six distinct TME archetypes based on their multicellular compositions,and find that patients with different TME archetypes responded differently to anti-PD-1 therapy.Finally,we find that classifying patients based on the gene expression signature derived from TME archetypes predicts anti-PD-1 therapy response across multiple validation cohorts.Conclusions:Our results demonstrate the utility of multiplex proteomic imaging technologies in studying complex molecular events in a spatially resolved manner for the development of new strategies for patient stratification and treatment outcome prediction. |
URI | http://hdl.handle.net/20.500.11897/672402 |
Appears in Collections: | 北京肿瘤医院 |