Zhang BL, Gao W, He L, Liu XT, Wang ZM, Tan L. Functional heterogeneity and clinical implications of CD4+ T cell subtypes in high-grade serous ovarian carcinoma. World J Clin Oncol 2025; 16(5): 104138 [DOI: 10.5306/wjco.v16.i5.104138]
Corresponding Author of This Article
Li Tan, MD, Associate Professor, Chief Physician, Department of Obstetrics and Gynecology, The Second People's Hospital of Hunan Province (Brain Hospital of Hunan Province), No. 427 Section 3, Furong Middle Road, Changsha 410007, Hunan Province, China. tanli2022@163.com
Research Domain of This Article
Oncology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Oncol. May 24, 2025; 16(5): 104138 Published online May 24, 2025. doi: 10.5306/wjco.v16.i5.104138
Functional heterogeneity and clinical implications of CD4+ T cell subtypes in high-grade serous ovarian carcinoma
Bei-Lei Zhang, Wei Gao, Ling He, Xiao-Ting Liu, Zhong-Ming Wang, Li Tan
Bei-Lei Zhang, Xiao-Ting Liu, Li Tan, Department of Obstetrics and Gynecology, The Second People's Hospital of Hunan Province (Brain Hospital of Hunan Province), Changsha 410007, Hunan Province, China
Wei Gao, Department of Traumatic Orthopedics, The Second People's Hospital of Hunan Province (Brain Hospital of Hunan Province), Changsha 410007, Hunan Province, China
Ling He, Department of Obstetrics and Gynecology, Second Xiangya Hospital, Changsha 410011, Hunan Province, China
Zhong-Ming Wang, Epilepsy Center, The Second People's Hospital of Hunan Province (Brain Hospital of Hunan Province), Changsha 410007, Hunan Province, China
Author contributions: Zhang BL, Gao W, and Tan L conceived and designed the study. Zhang BL and He L conducted the data collection and analysis; Liu XT and Wang ZM performed the single-cell RNA sequencing data processing and bioinformatics analyses; Gao W and He L contributed to the interpretation of results and preparation of figures; Zhang BL drafted the manuscript, and all authors critically reviewed and revised the manuscript for intellectual content; Tan L supervised the study.
Supported by The Natural Science Foundation of Hunan Province, China, No. 2022JJ30329.
Institutional review board statement: This study utilized data from publicly available databases and did not involve human participants, samples, or tissues. Therefore, approval from an Institutional Review Board was not required.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest related to this work. No financial, personal, or professional relationships have influenced the research, analysis, or conclusions presented in this manuscript.
Data sharing statement: The datasets generated and analyzed during this study can be obtained by contacting the corresponding author.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Li Tan, MD, Associate Professor, Chief Physician, Department of Obstetrics and Gynecology, The Second People's Hospital of Hunan Province (Brain Hospital of Hunan Province), No. 427 Section 3, Furong Middle Road, Changsha 410007, Hunan Province, China. tanli2022@163.com
Received: December 23, 2024 Revised: February 21, 2025 Accepted: April 15, 2025 Published online: May 24, 2025 Processing time: 148 Days and 20.5 Hours
Abstract
BACKGROUND
High-grade serous ovarian carcinoma (HGSOC) is among the most lethal gynecological malignancies, characterized by late-stage diagnosis, extensive peritoneal dissemination, and limited treatment options, resulting in poor survival outcomes. The tumor microenvironment plays a critical role in disease progression and therapy resistance, with CD4+ T cells exhibiting significant plasticity and functional heterogeneity. Regulatory T cells (Tregs) are particularly implicated in immune suppression and tumor evasion. However, the spatial distribution, functional states, and prognostic significance of CD4+ T cell subtypes in HGSOC remain poorly understood.
AIM
To characterize the functional heterogeneity and tissue-specific distributions of CD4+ T cell subtypes in HGSOC and identify biomarkers for therapy.
METHODS
We analyzed single-cell RNA sequencing (scRNA-seq) data from 42 HGSOC patients, examining samples collected from adnexal tissues and ascites. CD4+ T cells were identified and classified into subtypes using unsupervised clustering and marker gene analysis. Functional profiling was performed using pathway enrichment, differential expression analysis, and functional signature scoring. Kaplan-Meier survival and Cox proportional hazards modeling were conducted to evaluate the prognostic value of CD4+ T cell subtypes.
RESULTS
Distinct distributions of CD4+ T cell subtypes were identified between adnexal tissues and ascites. Naive CD4+ T cells were predominant in ascites, while Tregs and CXCL13-expressing CD4+ T cells were enriched in adnexal tissues. Tregs were further categorized into four subtypes (Treg1, Treg2, Treg3, and TISG), each exhibiting unique molecular signatures and tissue-specific adaptations. Treg3 cells, enriched in adnexal tissues, were characterized by high levels of activation and exhaustion markers, correlating with poor clinical outcomes in HGSOC patients.
CONCLUSION
Treg3 cells drive immune suppression and tumor progression in HGSOC, making them a key immunotherapy target. Their adnexal enrichment highlights the need for tissue-specific immune profiling in precision treatment.
Core Tip: This study uncovers the functional heterogeneity of CD4+ T cell subtypes in high-grade serous ovarian carcinoma (HGSOC), revealing their tissue-specific distributions and roles within the tumor microenvironment. Regulatory T cells (Tregs), particularly Treg3 cells, were identified as key immunosuppressive players enriched in adnexal tissues, correlating with poor prognosis and reduced immunotherapy response. By integrating single-cell RNA sequencing data, we provide novel insights into immune evasion mechanisms and identify Treg3 cells as potential therapeutic targets. These findings advance our understanding of HGSOC immunity and offer pathways for developing personalized immunotherapies.
