An atlas of genetic effects on cellular composition of the tumor microenvironment.

Autor: Cai Y; Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin hospital of Wuhan University, Department of Gastrointestinal Oncology, Zhongnan Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, China., Lu Z; Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin hospital of Wuhan University, Department of Gastrointestinal Oncology, Zhongnan Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, China., Chen C; Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin hospital of Wuhan University, Department of Gastrointestinal Oncology, Zhongnan Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, China., Zhu Y; Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin hospital of Wuhan University, Department of Gastrointestinal Oncology, Zhongnan Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, China., Chen Z; Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, China., Wu Z; Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, China., Peng J; Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, China., Zhu X; Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, China., Liu Z; Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, China., Li B; Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, China., Zhang M; Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, China., Huang J; Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, China., Li Y; Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, China., Liu Y; Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, China., Ma Q; Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, China., He C; Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, China., Chen S; Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, China., Tian W; Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, China., Fan L; Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, China., Ning C; Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, China., Geng H; Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, China., Xu B; Cancer Center, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, China., Li H; Department of Gastrointestinal Cancer Research Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China., Zhu X; Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan, China., Fang J; Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China., Wang X; Department of Cancer Epidemiology, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Henan Engineering Research Center of Cancer Prevention and Control, Henan International Joint Laboratory of Cancer Prevention, Zhengzhou, China., Zhang S; Department of Cancer Epidemiology, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Henan Engineering Research Center of Cancer Prevention and Control, Henan International Joint Laboratory of Cancer Prevention, Zhengzhou, China., Jin M; Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China., Huang C; Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China., Yang X; Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China., Tian J; Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin hospital of Wuhan University, Department of Gastrointestinal Oncology, Zhongnan Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, China. tianjb@whu.edu.cn., Miao X; Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin hospital of Wuhan University, Department of Gastrointestinal Oncology, Zhongnan Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, China. xpmiao@whu.edu.cn.; Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, China. xpmiao@whu.edu.cn.; Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China. xpmiao@whu.edu.cn.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2024 Oct; Vol. 25 (10), pp. 1959-1975. Date of Electronic Publication: 2024 Sep 02.
DOI: 10.1038/s41590-024-01945-3
Abstrakt: Deciphering the composition of the tumor microenvironment (TME) is critical for understanding tumorigenesis and to design immunotherapies. In the present study, we mapped genetic effects on cell-type proportions using single-cell and bulk RNA sequencing data, identifying 3,494 immunity quantitative trait loci (immunQTLs) across 23 cancer types from The Cancer Genome Atlas. Functional annotation revealed regulatory potential and we further assigned 1,668 genes that regulate TME composition. We constructed a combined immunQTL map by integrating data from European and Chinese colorectal cancer (CRC) samples. A polygenic risk score that incorporates these immunQTLs and hits on a genome-wide association study outperformed in CRC risk stratification within 447,495 multiethnic individuals. Using large-scale population cohorts, we identified that the immunQTL rs1360948 is associated with CRC risk and prognosis. Mechanistically, the rs1360948-G-allele increases CCL2 expression, recruiting regulatory T cells that can exert immunosuppressive effects on CRC progression. Blocking the CCL2-CCR2 axis enhanced anti-programmed cell death protein 1 ligand therapy. Finally, we have established a database (CancerlmmunityQTL2) to serve the research community and advance our understanding of immunogenomic interactions in cancer pathogenesis.
(© 2024. Springer Nature America, Inc.)
Databáze: MEDLINE
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