REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1643533
This article is part of the Research TopicExploring immune low-response states through single-cell technologies and spatial transcriptomicsView all 17 articles
Characteristics of the Tumor Microenvironment and Potential Immunotherapy Strategies in Renal Cell Carcinoma
Provisionally accepted
- 1Department of Nephrology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- 2Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- 3Department of Hematology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- 4Department of Nephrology, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai, China
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Renal cell carcinoma (RCC) is a highly vascularized and immunogenic malignancy with a complex tumor microenvironment (TME) that shapes disease progression and therapeutic resistance. Despite advances in immune checkpoint inhibitors (ICIs) and targeted therapies, clinical responses remain heterogeneous, underscoring the need for a deeper understanding of RCC immunobiology. This review comprehensively examines the immunosuppressive TME of RCC, emphasizing the roles of cytotoxic and immunosuppressive immune cells, carcinoma-associated fibroblasts (CAFs), abnormal vasculature, and extracellular matrix (ECM) remodeling in fostering immune evasion. This review summarized emerging biomarkers—including PD-L1 expression, tumor mutational burden (TMB), gene mutations, and immune-based subtypes—that may predict ICI response. Furthermore, we evaluate current immunotherapeutic strategies, such as ICIs, combination therapies, and novel approaches targeting immunosuppressive cells and metabolic pathways. While combination therapies have improved outcomes, challenges like toxicity and resistance persist, necessitating biomarker-driven patient stratification and optimized treatment sequencing. Future directions should focus on deciphering TME heterogeneity and developing precision immunotherapy strategies to enhance clinical efficacy in RCC.
Keywords: Renal cell carcinoma, Tumor Microenvironment, Immunosuppressive cells, biomarkers, Immunotherapy, combined targeted/immunotherapy
Received: 09 Jun 2025; Accepted: 15 Aug 2025.
Copyright: © 2025 Wen, Zheng, Zhu, Wang and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Ling Wang, Department of Nephrology, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai, China
Dongping Chen, Department of Nephrology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.