Open Access

REVIEW

Immunomodulatory behavior of CircRNAs in tumor microenvironment

HAISU LIANG^1,2,#, WEI YAN^3,#, ZHI LIU^1,4, YUNBO HE^1,2,5, JIAO HU¹, ZHIWEI SHU¹, HUIHUANG LI¹, BELAYDI OTHMANE¹, WENBIAO REN^1,6, CHAO QUAN¹, DONGXU QIU¹, MINFENG CHEN¹, WEI XIONG⁵, BINGNAN ZHANG^1,*, PEIHUA LIU^1,2,*

1 Department of Urology, Xiangya Hospital, Central South University, Changsha, 410000, China
2 National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410000, China
3 Department of Urology, Shimen Hospital of TCM, Changde, 415300, China
4 Department of Urology, The Second Affiliated Hospital, Guizhou Medical University, Kaili, 556000, China
5 NHC Key Laboratory of Carcinogenesis, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China
6 George Whipple Lab for Cancer Research, University of Rochester Medical Institute, Rochester, NY 14627, USA

* Corresponding Authors: BINGNAN ZHANG. Email: ; PEIHUA LIU. Email:
# These two authors contributed equally to this work

Oncology Research 2025, 33(5), 1105-1119. https://doi.org/10.32604/or.2024.054623

Received 03 June 2024; Accepted 13 November 2024; Issue published 18 April 2025

Abstract

Circular RNAs (circRNAs) are a type of non coding RNA that possess unique single stranded circular structures formed through reverse splicing mechanisms. Due to the lack of a free end that is typically susceptible to degradation by nucleases, circular RNAs exhibit resistance to ribonuclease R, making them highly stable in eukaryotic cells. The complex relationship between circRNA dysregulation and various pathophysiological conditions, especially cancer. Tumor microenvironment (TME) is a collective term for various components surrounding tumors and is an important factor affecting tumor development. Simultaneous infiltration of TME by different types of immune cells; These immune cells interact with the TME, collectively forming the so-called “tumor immune microenvironment”. The complex interactions between tumor cells and TME profoundly affect the behavior of malignant tumors, and circRNAs derived from tumor cells and TME cell components have become important mediators of immune response and evasion within the TME. CircRNAs can directly or indirectly regulate immune cells, thereby modulating anti-tumor immunity. This review highlights how circRNAs, especially those encapsulated in extracellular vesicles like exosomes, influence the differentiation, chemotaxis, and anti-tumor immune functions of immune cells within the TME. Metabolic reprogramming plays an important role in this process. The process of circRNAs regulating tumor immunity is affected by multiple factors, such as hypoxia and viral infection. This review emphasizes the roles of the interaction between circRNAs and the TME in tumor immune regulation and prospects the guiding significance of circRNAs in tumor immune checkpoint therapy.

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Keywords

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