Human leukocyte antigen DR alpha inhibits renal cell carcinoma progression by promoting the polarization of M2 macrophages to M1 via the NF-κB pathway.

Autor: Xiong F; Urology Surgery Department, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China. Electronic address: 15504627313@163.com., Wang B; Urology Surgery Department, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China. Electronic address: wangbowen@hrbmu.edu.cn., Zhang H; Urology Surgery Department, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China. Electronic address: doczhanghaoxun@163.com., Zhang G; Urology Surgery Department, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China. Electronic address: guoling_zhang@163.com., Liu Y; Urology Surgery Department, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China. Electronic address: 707885664@qq.com., Liu Y; Department of Gynecological Radiotherapy, Harbin Medical University Cancer Hospital, Harbin 150081, China. Electronic address: liu_yujie1011@163.com., Wang C; Urology Surgery Department, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China. Electronic address: wangchunyang@hrbmu.edu.cn.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2025 Jan 10; Vol. 144, pp. 113706. Date of Electronic Publication: 2024 Dec 03.
DOI: 10.1016/j.intimp.2024.113706
Abstrakt: Human leukocyte antigen DR alpha (HLA-DRA) is recognized for its inhibitory effect on the progression of clear cell renal cell carcinoma (ccRCC); high HLA-DRA expression levels are positively correlated with improved prognosis in patients with ccRCC. In this study, we evaluated HLA-DRA expression in ccRCCs, its effects on tumor-associated macrophage recruitment, and the influence of polarization. Clinical cohort analyses revealed that elevated HLA-DRA expression in ccRCC cells was correlated with enhanced tumor infiltration by M1-type macrophages. In addition, ccRCC prognosis was predicted by combining HLA-DRA expression level analysis and the M1/M2 macrophage ratio. In vitro studies demonstrated that ccRCC cells with increased HLA-DRA expression promoted THP-1 cell migration and induced macrophage polarization toward the M1 phenotype. The effect was further substantiated in a mouse xenograft model in which an increase in M1 macrophages was observed. In addition, co-culturing macrophages with the supernatant from cells overexpressing HLA-DRA induced the expression of proteins associated with both M1 and M2 macrophage polarization. HLA-DRA was intricately linked to the expression and secretion of chemokines, including CCL2, CCL5, MIP-1ɑ, and CXCL-10. Moreover, the NF-κB pathway activation promoted polarization to M1 macrophages. This study shows that HLA-DRA and the M1/M2 ratio are indicators of favorable prognosis in patients with ccRCC. HLA-DRA promotes M1-like polarization by regulating NF-κB, which can be used as a therapeutic target to enhance anti-tumor immunity.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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