REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1656925
This article is part of the Research TopicUnleashing Immunity against Cancer: New Horizons in ImmunotherapyView all 4 articles
Enhancing Natural Killer Cell Anti-Tumour Activity through Macrophage Manipulation
Provisionally accepted
- University of Southampton, Southampton, United Kingdom
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
The tumour microenvironment (TME) is a complex and dynamic environment containing diverse cellular, stromal and soluble factors, that collectively influence cancer progression, immune evasion and therapeutic resistance. Among the immune components of the TME, macrophages and natural killer (NK) cells are key players, whose interactions, particularly their crosstalk, critically shape antitumour immunity. The macrophage-NK cell interplay can either promote or suppress immune responses depending on the context, representing both a challenge and a therapeutic opportunity. NK cells are key effectors capable of recognising and eliminating malignant cells without prior sensitisation, whereas macrophages exhibit remarkable plasticity, functioning as either promoters or suppressors of tumour immunity depending on their activation state. This review focuses on current strategies to harness macrophages in cancer therapy, including phenotype repolarisation, selective depletion, and disruption or enhancement of the macrophage-NK cell crosstalk to enhance NK cellmediated tumour surveillance. Finally, we highlight emerging technologies, such as single-cell RNA sequencing, spatial transcriptomics, and proteomics, as powerful tools to elucidate the dynamic interplay between macrophages and NK cells and inform the next generation of immunotherapeutic interventions.
Keywords: Macrophages, Natural Killer cells, immune crosstalk, Cancer, Immunotherapy
Received: 30 Jun 2025; Accepted: 11 Aug 2025.
Copyright: © 2025 Palmer, Khakoo, Sanchez-Elsner and Vallejo. 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:
Salim Iqbal Khakoo, University of Southampton, Southampton, United Kingdom
Andres F Vallejo, University of Southampton, Southampton, United Kingdom
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.