Identification of immune subtypes of cervical squamous cell carcinoma predicting prognosis and immunotherapy responses

Journal of Translational Medicine

Jinyi Lang¹  Shun Lu¹  Yimin Li²  Xinhao Peng²  Shubin Wang² 

[1] Department of Radiation Oncology, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, No.55, South Renmin Avenue Fourth Section, 610041, Chengdu City, Sichuan Province, People’s Republic of China;Radiation Oncology Key Laboratory of Sichuan Province, No.55, South Renmin Avenue Fourth Section, 610041, Chengdu City, Sichuan Province, People’s Republic of China;School of Medicine, University of Electronic Science and Technology of China, No.2006, Xiyuan Avenue, High-Tech Zone (West District), 611731, Chengdu City, Sichuan Province, People’s Republic of China;

关键词: Cervical squamous cell cancer;    Nonnegative matrix factorization;    Immune checkpoint inhibitors;    Subtype;    Immunophenotype;    Immunotherapy response;   

DOI  :  10.1186/s12967-021-02894-3

来源: Springer

【 摘 要 】

BackgroundThe main limitation of current immune checkpoint inhibitors (ICIs) in the treatment of cervical cancer comes from the fact that it benefits only a minority of patients. The study aims to develop a classification system to identify immune subtypes of cervical squamous cell carcinoma (SCC), thereby helping to screen candidates who may respond to ICIs.MethodsA real-world cervical SCC cohort of 36 samples were analyzed. We used a nonnegative matrix factorization (NMF) algorithm to separate different expression patterns of immune-related genes (IRGs). The immune characteristics, potential immune biomarkers, and somatic mutations were compared. Two independent data sets containing 555 samples were used for validation.ResultsTwo subtypes with different immunophenotypes were identified. Patients in sub1 showed favorable progression-free survival (PFS) and overall survival (OS) in the training and validation cohorts. The sub1 was remarkably related to increased immune cell abundance, more enriched immune activation pathways, and higher somatic mutation burden. Also, the sub1 group was more sensitive to ICIs, while patients in the sub2 group were more likely to fail to respond to ICIs but exhibited GPCR pathway activity. Finally, an 83-gene classifier was constructed for cervical SCC classification.ConclusionThis study establishes a new classification to further understand the immunological diversity of cervical SCC, to assist in the selection of candidates for immunotherapy.

【 授权许可】

CC BY