Dissecting cellular states of infiltrating microenvironment cells in melanoma by integrating single-cell and bulk transcriptome analysis

作者全名："Shi, Aiai; Yan, Min; Pang, Bo; Pang, Lin; Wang, Yihan; Lan, Yujia; Zhang, Xinxin; Xu, Jinyuan; Ping, Yanyan; Hu, Jing"

作者地址："[Shi, Aiai] Guilin Med Univ, Sch Intelligent Med & Biotechnol, Guilin 541100, Guangxi, Peoples R China; [Yan, Min] Chongqing Med Univ, Coll Basic Med, Dept Immunol, Chongqing 400010, Peoples R China; [Pang, Bo; Pang, Lin; Wang, Yihan; Lan, Yujia; Zhang, Xinxin; Xu, Jinyuan; Ping, Yanyan; Hu, Jing] Harbin Med Univ, Coll Bioinformat Sci & Technol, Harbin 150081, Heilongjiang, Peoples R China"

通信作者："Xu, JY; Ping, YY; Hu, J (通讯作者)，Harbin Med Univ, Coll Bioinformat Sci & Technol, Harbin 150081, Heilongjiang, Peoples R China."

来源：BMC IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001121683000001

JCR分区：Q3

影响因子：2.9

年份：2023

卷号：24

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Cell states; Microenvironment; Immune phenotype; Immunotherapy; Melanoma

摘要："BackgroundCellular states of different immune cells can affect the activity of the whole immune microenvironment.MethodsHere, leveraging reference profiles of microenvironment cell states that were constructed based on single-cell RNA-seq data of melanoma, we dissected the composition of microenvironment cell states across 463 skin cutaneous melanoma (SKCM) bulk samples through CIBERSORT-based deconvolution of gene expression profiles and revealed high heterogeneity of their distribution. Correspondence analysis on the estimated cellular fractions of melanoma bulk samples was performed to identify immune phenotypes. Based on the publicly available clinical survival and therapy data, we analyzed the relationship between immune phenotypes and clinical outcomes of melanoma.ResultsBy analysis of the relationships among those cell states, we further identified three distinct tumor microenvironment immune phenotypes: ""immune hot/active"", ""immune cold-suppressive"" and ""immune cold-exhausted"". They were characterized by markedly different patterns of cell states: most notably the CD8 T Cytotoxic state, CD8 T Mixed state, B non-regulatory state and cancer-associated fibroblasts (CAFs), depicting distinct types of antitumor immune response (or immune activity). These phenotypes had prognostic significance for progression-free survival and implications in response to immune therapy in an independent cohort of anti-PD1 treated melanoma patients.ConclusionsThe proposed strategy of leveraging single-cell data to dissect the composition of microenvironment cell states in individual bulk tumors can also extend to other cancer types, and our results highlight the importance of microenvironment cell states for the understanding of tumor immunity."

基金机构："National Natural Science Foundation of China [31900478, 31601076, 32000459, 81802926, 31801116]; Special funds for the construction of higher education in Heilongjiang Province [UNPYSCT-2018068]; Heilongjiang Postdoctoral Scientific Research Developmental Fund [LBH-Q20147]; China Postdoctoral Science Foundation [2018M641842, 2017M621295]; Postdoctoral Science Foundation of Chongqing Municipal Natural Science Foundation [CSTB2023NSCQ-BHX0152]"

基金资助正文："This work was supported in part by the the National Natural Science Foundation of China [Grant Nos. 31900478, 31601076, 32000459, 81802926, 31801116], the Special funds for the construction of higher education in Heilongjiang Province [Grant No. UNPYSCT-2018068], the Heilongjiang Postdoctoral Scientific Research Developmental Fund [LBH-Q20147], the China Postdoctoral Science Foundation [2018M641842, 2017M621295], the Postdoctoral Science Foundation of Chongqing Municipal Natural Science Foundation (CSTB2023NSCQ-BHX0152)."