A single-cell atlas reveals immune heterogeneity in anti-PD-1-treated non-small cell lung cancer
Anti-PD-(L)1 treatment is standard for non-small cell lung cancer (NSCLC), but patients show variable responses to the same regimen. The tumor immune microenvironment (TIME) is associated with immunotherapy response, yet the heterogeneous underlying therapeutic outcomes remain underexplored. We applied single-cell RNA and TCR sequencing (scRNA/TCR-seq) to analyze surgical tumor samples from 234 NSCLC patients post-neoadjuvant chemo-immunotherapy. Analyses revealed five distinct TIME subtypes with varying major pathological response (MPR) rates. MPR patients had elevated levels of FGFBP2<sup>+</sup> NK/NK-like T cells, memory B cells, or effector T cells, while non-MPR patients showed higher CCR8<sup>+</sup> Tregs. T cell clonal expansion analyses unveiled heterogeneity in non-MPR patients, marked by varying expansions of Tex-relevant cells and CCR8<sup>+</sup> Tregs. Precursor exhausted T cells (Texp cells) correlated with recurrence-free survival, identifying a patient subgroup with reduced recurrence risk despite lack of MPR. Our study dissects TIME heterogeneity in response to chemoimmunotherapy, offering insights for NSCLC management.
Authors
- Yuxuan Sun (ORCID: https://orcid.org/0000-0002-7057-3459)
- Deping Zhao (ORCID: https://orcid.org/0000-0003-0109-5171)
- Xiangjie Li (ORCID: https://orcid.org/0000-0002-9600-8984)
- Lishan Peng
- Bolun Zhou (ORCID: https://orcid.org/0000-0001-8143-4852)
- Zedao Liu
- Sijin Cheng (ORCID: https://orcid.org/0000-0002-2565-7127)
- Chang Zou (ORCID: https://orcid.org/0000-0002-2003-7834)
- Minglei Yang (ORCID: https://orcid.org/0000-0001-9957-7608)
- Qianqian Gao (ORCID: https://orcid.org/0000-0002-7022-139X)
- Liang Zhao (ORCID: https://orcid.org/0000-0003-3643-134X)
- Hui Peng (ORCID: https://orcid.org/0000-0002-5838-5922)
- Yongjun Guo (ORCID: https://orcid.org/0000-0003-1641-2969)
- Honghao Fu (ORCID: https://orcid.org/0000-0002-1934-3391)
- Zhenlin Yang (ORCID: https://orcid.org/0000-0002-6650-7782)
- Xiaoyan Liu (ORCID: https://orcid.org/0000-0002-9920-2942)
- Zemin Zhang (ORCID: https://orcid.org/0000-0002-3182-7153)
- Chang Liu (ORCID: https://orcid.org/0000-0002-6273-6465)
- Guangjian Zhang (ORCID: https://orcid.org/0000-0003-0663-6256)
- Zhigang Zhao (ORCID: https://orcid.org/0000-0003-3147-8544)
- Wen‐Zhao Zhong (ORCID: https://orcid.org/0000-0002-8917-8635)
- Zhigang Tian (ORCID: https://orcid.org/0000-0002-5512-6378)
- Shugeng Gao (ORCID: https://orcid.org/0000-0003-3171-5319)
- Wenjie Zhang (ORCID: https://orcid.org/0000-0003-1765-1945)
- Yang Li (ORCID: https://orcid.org/0000-0001-9612-2704)
- Lei Zhang (ORCID: https://orcid.org/0000-0003-4498-8236)
- Yongjie Wang (ORCID: https://orcid.org/0000-0002-4059-5585)
- Xiaowei Chen (ORCID: https://orcid.org/0009-0009-2079-8105)
- Chao Zhang (ORCID: https://orcid.org/0000-0003-0399-1201)
- Dingcheng Yi
- Yi-Long Lung Cancer Wu (ORCID: https://orcid.org/0000-0002-3611-0258)
- Li‐Xu Yan (ORCID: https://orcid.org/0000-0002-5584-4265)
- Yufei Bo
- Chen Chang (ORCID: https://orcid.org/0000-0001-8408-0906)
- Ya‐Wen Chen (ORCID: https://orcid.org/0000-0003-2382-8444)
- Qingyuan Cai (ORCID: https://orcid.org/0000-0002-4600-4643)
- Qi Lu
- Junqi Wu (ORCID: https://orcid.org/0000-0001-6560-3281)
- Xueda Hu (ORCID: https://orcid.org/0000-0002-8705-1518)
- Wei Tang (ORCID: https://orcid.org/0000-0002-4573-3502)
- Xiaoshi Ma
- Ben‐Yuan Jiang
- Yang Qu (ORCID: https://orcid.org/0000-0002-8969-8278)
- Guangyu Bai (ORCID: https://orcid.org/0009-0002-6356-5706)
- Linnan Zhu
- Shun He
- Fengwei Tan
- Long Xu
- Hongtao Fan
- Wanting Zhang (ORCID: https://orcid.org/0000-0002-9750-8331)
- Yunlang She (ORCID: https://orcid.org/0000-0003-2841-1250)
- Yu Zhang (ORCID: https://orcid.org/0009-0005-6052-7087)
Institutions
- Qingdao University (CN)
- Tongji University (CN)
- University of Science and Technology of China (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Peking University (CN)
- Ningbo No. 2 Hospital (CN)
- Shenzhen Bay Laboratory (CN)
- Affiliated Hospital of Qingdao University (CN)
- First Affiliated Hospital of Xi'an Jiaotong University (CN)
- Shanghai Pulmonary Hospital (CN)
- Henan Cancer Hospital (CN)
- Guangdong Academy of Medical Sciences (CN)
- Analytical Biosciences (China) (CN)
- Guangdong Provincial People's Hospital (CN)
- First Affiliated Hospital of Zhengzhou University (CN)
Publication Details
- Journal
- Cell
- Published
- 2025-03-27
- DOI
- https://doi.org/10.1016/j.cell.2025.03.018
- Citations
- 71
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 74.22