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Single-cell profiling reveals the heterogeneity of NK cells during anti-PD-1 therapy in non-small-cell lung cancer

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机构： [1]Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China; School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China. [2]Department of Respiratory and Critical Care Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China; Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu 610072, China. [3]Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu 610072, China. [4]Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China. Electronic address: lizayangyang@hotmail.com. [5]School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China. Electronic address: shiying_uestc@uestc.edu.cn.

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The efficacy of immune checkpoint inhibitors remains limited in non-small cell lung cancer (NSCLC). Natural killer (NK) cells serve as the key element of innate immunity and play an important role in anti-tumor immunity, the impact of NK cells on efficacy of anti-PD-1 therapy in NSCLC is worth exploring.We analyzed single-cell transcriptome data derived from biopsies of NSCLC patients receiving anti-PD-1 treatment. Immune cell subtypes were identified and further cell-cell communication were analyzed and verified.We observed totally 6 distinct NK cells clusters in NSCLC infiltrating immune cells. It's worth noting that enrichment of immature NK cells was found in responsive group. A series of marker genes of immature NK cells were associated with anti-PD-1 response and related to immune regulation processes such as antigen processing, Th1, Th17 cells activation. Moreover, effector CD8+ T cells were significantly enriched in responsive group and showed similar trajectories with immature NK cells. Cell-cell communication analysis showed that immature NK cells showed strong interactions with Th17 cells and effector CD8+ T cells. Furthermore, when validating the expression of immature NK cells marker genes, we found that CXCR4 was associated with enriched infiltration of CD8+ T cells.In conclusion, immature NK cells may facilitate the efficacy of anti-PD-1 therapy by interacting with Th1 cells, Th17 cells and enhancing infiltration of effector CD8+ T cells. Our data suggested that NK cells could be a promising target to improve the prognosis of NSCLC patients.Copyright © 2023. Published by Elsevier B.V.

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大类 | 2 区

医学

小类 | 2 区免疫学 2 区药学

最新[2023]版：

大类 | 2 区

医学

小类 | 2 区免疫学 2 区药学

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出版当年[2023]版：

Q1 PHARMACOLOGY & PHARMACY Q2 IMMUNOLOGY

最新[2023]版：

Q1 PHARMACOLOGY & PHARMACY Q2 IMMUNOLOGY

影响因子： 4.8 最新[2023版] 5 最新五年平均 4.8 出版当年[2023版] 5 出版当年五年平均 5.6 出版前一年[2022版]

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第一作者机构： [1]Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China; School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.

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