Multi-dimensional characterization of immunological profiles in small cell lung cancer uncovers clinically relevant immune subtypes with distinct prognoses and therapeutic vulnerabilities

doi:10.1016/j.phrs.2023.106844

科研成果详情

题名	Multi-dimensional characterization of immunological profiles in small cell lung cancer uncovers clinically relevant immune subtypes with distinct prognoses and therapeutic vulnerabilities
作者	Yang, Lin 1; Zhang, Zicheng 2; Dong, Jiyan 1; Zhang, Yibo2; Yang, Zijian2; Guo, Yiying 3; Sun, Xujie 1; Li, Junling 3; Xing, Puyuan 3; Ying, Jianming 1; Zhou, Meng2
发表日期	2023-08
发表期刊	Pharmacological research 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	Digital spatial profiling Formalin-fixed-paraffin-embedded Immune subtypes Small cell lung cancer Tumor microenvironment
摘要	Small-cell lung cancer (SCLC) is generally considered a 'homogenous' disease, with little documented inter-tumor heterogeneity in treatment guidance or prognosis evaluation. The precise identification of clinically relevant molecular subtypes remains incomplete and their translation into clinical practice is limited. In this retrospective cohort study, we comprehensively characterized the immune microenvironment in SCLC by integrating transcriptional and protein profiling of formalin-fixation-and-paraffin-embedded (FFPE) samples from 29 patients. We identified two distinct disease subtypes: immune-enriched (IE-subtype) and immune-deprived (ID-subtype), displaying heterogeneity in immunological, biological, and clinical features. The IE-subtype was characterized by abundant immune infiltrate and elevated levels of interferon-alpha/gamma (IFNα/IFNγ) and inflammatory response, while the ID-subtype featured a complete lack of immune infiltration and a more proliferative phenotype. These two immune subtypes are associated with clinical benefits in SCLC patients treated with adjuvant therapy, with the IE-subtype exhibiting a more favorable response leading to improved survival and reduced disease recurrence risk. Additionally, we identified and validated a personalized prognosticator of immunophenotyping, the CCL5/CXCL9 chemokine index (CCI), using machine learning. The CCI demonstrated superior predictive abilities for prognosis and clinical benefits in SCLC patients, validated in our institute immunohistochemistry cohort and multicenter bulk transcriptomic data cohorts. In conclusion, our study provides a comprehensive and multi-dimensional characterization of the immune architecture of SCLC using clinical FFPE samples and proposes a new immune subtyping conceptual framework enabling risk stratification and the appropriate selection of individualized therapy.
资助项目	Special Project for Clinical and Translational Medicine Research of Chinese Academy of Medical Sciences [2021-12M-C, LC 2017 A20]; National Natural Science Foundation of China [2021-I2M-1-067]; Innovation Fund for Medical Sciences of Chinese Academy of Medical Sciences [T-B-062]; Cancer Foundation of China, Beijing Hope Marathon Foundation; [82172826]
出版者	ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
ISSN	1043-6618
EISSN	1096-1186
卷号	194
DOI	10.1016/j.phrs.2023.106844
页数	13
WOS类目	Pharmacology & Pharmacy
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:001038132100001
收录类别	PUBMED ; SCIE ; SCOPUS
在线发表日期	2023-07
URL	查看原文
PubMed ID	37392900
SCOPUSEID	2-s2.0-85164332944
通讯作者地址	[Xing, Puyuan]Department of Medical Oncology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,100021,China
Scopus学科分类	Pharmacology
TOP期刊	TOP期刊
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/181268
专题	仁济学院_眼视光、生物医学工程学部
通讯作者	Xing, Puyuan
作者单位	1.Department of Pathology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,100021,China; 2.School of Biomedical Engineering,Eye Hospital,Wenzhou Medical University,Wenzhou,325027,China; 3.Department of Medical Oncology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,100021,China
推荐引用方式 GB/T 7714	Yang, Lin,Zhang, Zicheng,Dong, Jiyan,et al. Multi-dimensional characterization of immunological profiles in small cell lung cancer uncovers clinically relevant immune subtypes with distinct prognoses and therapeutic vulnerabilities[J]. Pharmacological research,2023,194.
APA	Yang, Lin., Zhang, Zicheng., Dong, Jiyan., Zhang, Yibo., Yang, Zijian., ... & Zhou, Meng. (2023). Multi-dimensional characterization of immunological profiles in small cell lung cancer uncovers clinically relevant immune subtypes with distinct prognoses and therapeutic vulnerabilities. Pharmacological research, 194.
MLA	Yang, Lin,et al."Multi-dimensional characterization of immunological profiles in small cell lung cancer uncovers clinically relevant immune subtypes with distinct prognoses and therapeutic vulnerabilities".Pharmacological research 194(2023).