REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicPrecision Immuno-Oncology: Harnessing Novel Drug Development, Biomarkers, and Nanoparticle-Based Therapeutic Platforms to Overcome Cancer ResistanceView all articles
Targeting Cancer via Macrophage-Derived Exosomal miRNAs: Implications for Tumor Progression and Resistance
Provisionally accepted
Prasanna Srinivasan Ramalingam1
Muhammad Afzal2
M Arockia Babu3Rekha M M4Samir Sahoo5Surya Nath Pandey6Haider Ali7
Md Sadique Hussain8Gaurav Gupta10,9Janaki Ramaiah Mekala11*
Sivakumar Arumugam12*- 1School of Biosciences and Technology, Vellore Institute of Technology, Vellore, India
- 2Batterjee Medical College, Jeddah, Saudi Arabia
- 3GLA University, Mathura, India
- 4JAIN (Deemed-to-be University), Bengaluru, India
- 5Siksha O Anusandhan University Institute of Medical Sciences and SUM Hospital, Bhubaneswar, India
- 6Teerthanker Mahaveer University, Moradabad, India
- 7SIMATS Deemed University, Chennai, India
- 8Uttaranchal University, Dehradun, India
- 9Chitkara University, Rajpura, India
- 10Ajman University, Ajman, United Arab Emirates
- 11Vellore Institute of Technology,, vellore, India
- 12Vellore Institute of Technology, Vellore, India
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Recent studies on macrophages showed their contribution to tumorigenesis, progression, metastasis, and chemoresistance by influencing the local tumor microenvironment and cancer cells. Exosomes form a subset of extracellular vesicles and have played a major role in the interaction between cancer cells and macrophages. This review intends to discuss the existing literature on employing macrophage-derived exosomes as a vehicle for microRNA (miRNA) delivery in oncological applications. It will evaluate the molecular principles of this therapeutic approach and its capacity to enhance cancer therapy by elucidating problems like drug and radio-resistance. This review uniquely emphasizes the diagnostic and therapeutic potential of macrophage-derived exosomal miRNAs, summarizing current understandings into their molecular processes, tumor specificity, and strategies to overcome therapeutic resistance. This review synthesizes recent studies and evaluates how macrophage-derived exosomes and their miRNAs contribute to cancers. These vesicles are multipurpose tools that regulate tumor behaviour, considering they can regulate it through post-transcriptional regulation and protein phosphorylation. Such exosomes that are engineered can potentially introduce a novel dimension because they have the capability of delivering targeted oncogenic or tumor-suppressive miRNAs to overcome limitations of current cancer therapeutics, particularly drug and radioresistance. Engineered macrophage-derived exosomes may thus have the potential as a novel approach for cancer treatment and overcoming therapeutic resistance.
Keywords: Cancer biomarkers, exosomal miRNAs, macrophage-derived exosomes, therapeutic resistance, Tumor-associated macrophages, Tumor Microenvironment
Received: 11 Aug 2025; Accepted: 03 Nov 2025.
Copyright: © 2025 Ramalingam, Afzal, Babu, M M, Sahoo, Pandey, Ali, Hussain, Gupta, Mekala and Arumugam. 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:
Janaki Ramaiah Mekala, janakiramaiah.m@vit.ac.in
Sivakumar Arumugam, siva_kumar.a@vit.ac.in
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.