SYSTEMATIC REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1639334
This article is part of the Research TopicNon-coding RNAs in the tumoral microenvironment: mechanisms, regulatory networks and clinical applications in cancer immunityView all articles
The miRNA-Immune Axis in Bladder Cancer: Systematic Evidence for a New Era of Immunotherapy Precision
Provisionally accepted
Daniel-Vasile Dulf1
Gloria Ravegnini2*
Federico Manuel Giorgi2anamaria burnar1
Francesca Gorini2
Antonio De Leo2harisa lutichievici1
lucian oprita1cezar todirut1Tudor-Eliade Ciuleanu1
Camelia Alexandra Coada2- 1Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania
- 2University of Bologna, Bologna, Italy
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Introduction: Bladder cancer (BC) is a complex disease with patients showing widely variable responses to treatment. While immunotherapy has recently emerged as a promising alternative to the standard platinum-based chemotherapy especially for platinum resistant tumors, clinicians still lack reliable biomarkers to predict which patients will truly benefit from immunotherapy.Aim: This systematic review aimed to explore whether miRNAs could help decode the immune landscape of BC and serve as predictive biomarkers for immunotherapy response.Methods: A total of 3272 articles were systematically screened on medical databases, and narrowed down to 37 studies that examined the relationship between miRNAs, immune cell infiltration, and patient outcomes in BC. To further strengthen and validate our findings, we analyzed large-scale genomic data from The Cancer Genome Atlas (TCGA-BLCA).Results: A total of 104 different miRNAs appeared to shape the BC immune microenvironment. Some studies also linked miRNA expression with clinical outcomes such as BCG therapy response and prognosis, while others dissected the molecular pathways. Further analyses established miR-155, miR-142, and miR-146b, as key factors for CD4+ memory T cells and M1 macrophages infiltration. Notably, 49 miRNAs showed stage-specific expression differences in TCGA data, with 25 of them also significantly associated with progression-free interval or overall survival.Conclusion: miRNAs are emerging as powerful regulators of the immune microenvironment of BC. However, despite growing evidence, to date no studies have directly explored miRNA profiles in driving immunotherapeutic decisions. Our findings highlight the need for prospective studies to translate these molecular insights into personalized treatment strategies.
Keywords: Immune checkpoint inhibitor, Immunotherapy, Tumor immune infiltration, PD-L1, prognosis
Received: 01 Jun 2025; Accepted: 18 Aug 2025.
Copyright: © 2025 Dulf, Ravegnini, Giorgi, burnar, Gorini, De Leo, lutichievici, oprita, todirut, Ciuleanu and Coada. 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: Gloria Ravegnini, University of Bologna, Bologna, Italy
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