Multi-omic profiling highlights factors associated with resistance to immuno-chemotherapy in non-small-cell lung cancer.

Autor: Yan Y; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China., Sun D; Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital, School of Life Science and Technology, Tongji University, Shanghai, China.; Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China., Hu J; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China., Chen Y; State Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China., Sun L; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China., Yu H; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China., Xiong Y; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China., Huang Z; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China., Xia H; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China., Zhu X; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China., Bian D; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China., Sun F; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China., Hou L; Department of Pathology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China., Wu C; Department of Pathology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China., Fan OR; Stem Cell Translational Research Center, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China., Hu H; Central Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China., Zeng A; State Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China. azeng@sibcb.ac.cn., Zhang L; Central Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China. zhanglele@tongji.edu.cn., Sun YE; Stem Cell Translational Research Center, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China. yi.eve.sun@gmail.com., Wang C; Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital, School of Life Science and Technology, Tongji University, Shanghai, China. 08chenfeiwang@tongji.edu.cn.; Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China. 08chenfeiwang@tongji.edu.cn.; National Key Laboratory of Autonomous Intelligent Unmanned Systems, Tongji University, Shanghai, China. 08chenfeiwang@tongji.edu.cn.; Frontier Science Center for Intelligent Autonomous Systems, Tongji University, Shanghai, China. 08chenfeiwang@tongji.edu.cn., Zhang P; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China. zhangpeng1121@tongji.edu.cn.; Department of Thoracic Surgery, The First Affiliated Hospital of Shihezi University Medical College, Shihezi, China. zhangpeng1121@tongji.edu.cn.
Jazyk: angličtina
Zdroj: Nature genetics [Nat Genet] 2024 Dec 10. Date of Electronic Publication: 2024 Dec 10.
DOI: 10.1038/s41588-024-01998-y
Abstrakt: Although immune checkpoint blockade (ICB) therapies have shifted the treatment paradigm for non-small-cell lung cancer (NSCLC), many patients remain resistant. Here we characterize the tumor cell states and spatial cellular compositions of the NSCLC tumor microenvironment (TME) by analyzing single-cell transcriptomes of 232,080 cells and spatially resolved transcriptomes of tumors from 19 patients before and after ICB-chemotherapy. We find that tumor cells and secreted phosphoprotein 1-positive macrophages interact with collagen type XI alpha 1 chain-positive cancer-associated fibroblasts to stimulate the deposition and entanglement of collagen fibers at tumor boundaries, obstructing T cell infiltration and leading to poor prognosis. We also reveal distinct states of tertiary lymphoid structures (TLSs) in the TME. Activated TLSs are associated with improved prognosis, whereas a hypoxic microenvironment appears to suppress TLS development and is associated with poor prognosis. Our study provides novel insights into different cellular and molecular components corresponding to NSCLC ICB-chemotherapeutic responsiveness, which will benefit future individualized immuno-chemotherapy.
Competing Interests: Competing interests: The authors declare no competing interests.
(© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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