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已发表论文
CLEC3A 通过增强 PD-L1 的稳定性削弱 T 细胞的细胞毒性，从而促进管腔型乳腺癌的免疫逃逸和肿瘤进展
Authors Chen C, Li H, Liu Y, Zhang X, Sun Y, Li X
Received 9 April 2025
Accepted for publication 13 October 2025
Published 27 October 2025 Volume 2025:17 Pages 977—995
DOI https://doi.org/10.2147/BCTT.S533474
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 5
Editor who approved publication: Professor Harikrishna Nakshatri
Chen Chen,1– 3 Hongtao Li,2 Yuan Liu,2 Xiaojing Zhang,2 Yanfeng Sun,2 Xianming Li1,3
1Jinan University, Guangzhou, Guangdong, 510632, People’s Republic of China; 2Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, 233000, People’s Republic of China; 3Department of Radiation Oncology, The 2nd Clinical Medical College (Shenzhen People’s Hospital) of Jinan University, Shenzhen, Guangdong, 518020, People’s Republic of China
Correspondence: Xianming Li, Department of Radiation Oncology, The 2nd Clinical Medical College (Shenzhen People’s Hospital) of Jinan University, No. 1017 Dongmenbei Road, Luohu District, Shenzhen, Guangdong, 518020, People’s Republic of China, Email lxm1828@hotmail.com
Background: Luminal breast cancer (BC) is the most common subtype of BC. C-type lectin domain family 3 member A (CLEC3A) has been shown to promote malignant characteristics in BC cells, but the specific mechanisms are not well understood. This study aimed to explore the oncogenic role of CLEC3A in luminal BC and its potential mechanisms.
Methods: Transcriptomic data from GEO and TCGA databases were analyzed to identify differentially expressed genes in luminal BC. Kaplan–Meier curves were used to assess the prognostic value of CLEC3A in luminal BC, and CLEC3A expression was further validated in BC cell lines. Functional assays, including colony formation, wound healing, Transwell, and flow cytometry, were performed following CLEC3A knockdown or overexpression. The impact of CLEC3A on PD-L1 stability was analyzed by co-immunoprecipitation (co-IP) and Western blotting. The influence of CLEC3A on T cell activity was investigated by co-culturing CD8+ T cells with BC cells.
Results: CLEC3A expression was significantly upregulated in luminal BC patients and correlated with poor overall survival. In vitro, CLEC3A knockdown suppressed proliferation, migration, invasion and promoted apoptosis, whereas CLEC3A overexpression enhanced these malignant features. CLEC3A also regulated mRNA expression levels of key proliferation-related genes and immune factors, and it regulated the stability of PD-L1 protein in BC cells through ubiquitination. Additionally, CLEC3A knockdown increased tumor cell death and CD8⁺ T cell activity, while overexpression suppressed these responses.
Conclusion: CLEC3A promotes BC progression and immune evasion by regulating PD-L1 stability and inhibiting CD8⁺ T cell function. Targeting CLEC3A may enhance anti-tumor immunity and improve patient outcomes in luminal BC.
Keywords: luminal breast cancer, CLEC3A, cancer progression, PD-L1, ubiquitination, tumor immune microenvironment
1Jinan University, Guangzhou, Guangdong, 510632, People’s Republic of China; 2Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, 233000, People’s Republic of China; 3Department of Radiation Oncology, The 2nd Clinical Medical College (Shenzhen People’s Hospital) of Jinan University, Shenzhen, Guangdong, 518020, People’s Republic of China
Correspondence: Xianming Li, Department of Radiation Oncology, The 2nd Clinical Medical College (Shenzhen People’s Hospital) of Jinan University, No. 1017 Dongmenbei Road, Luohu District, Shenzhen, Guangdong, 518020, People’s Republic of China, Email lxm1828@hotmail.com
Background: Luminal breast cancer (BC) is the most common subtype of BC. C-type lectin domain family 3 member A (CLEC3A) has been shown to promote malignant characteristics in BC cells, but the specific mechanisms are not well understood. This study aimed to explore the oncogenic role of CLEC3A in luminal BC and its potential mechanisms.
Methods: Transcriptomic data from GEO and TCGA databases were analyzed to identify differentially expressed genes in luminal BC. Kaplan–Meier curves were used to assess the prognostic value of CLEC3A in luminal BC, and CLEC3A expression was further validated in BC cell lines. Functional assays, including colony formation, wound healing, Transwell, and flow cytometry, were performed following CLEC3A knockdown or overexpression. The impact of CLEC3A on PD-L1 stability was analyzed by co-immunoprecipitation (co-IP) and Western blotting. The influence of CLEC3A on T cell activity was investigated by co-culturing CD8+ T cells with BC cells.
Results: CLEC3A expression was significantly upregulated in luminal BC patients and correlated with poor overall survival. In vitro, CLEC3A knockdown suppressed proliferation, migration, invasion and promoted apoptosis, whereas CLEC3A overexpression enhanced these malignant features. CLEC3A also regulated mRNA expression levels of key proliferation-related genes and immune factors, and it regulated the stability of PD-L1 protein in BC cells through ubiquitination. Additionally, CLEC3A knockdown increased tumor cell death and CD8⁺ T cell activity, while overexpression suppressed these responses.
Conclusion: CLEC3A promotes BC progression and immune evasion by regulating PD-L1 stability and inhibiting CD8⁺ T cell function. Targeting CLEC3A may enhance anti-tumor immunity and improve patient outcomes in luminal BC.
Keywords: luminal breast cancer, CLEC3A, cancer progression, PD-L1, ubiquitination, tumor immune microenvironment