REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicImplications of senescence in cancer immunologyView all 5 articles
CELLULAR SENESCENCE IN THE INNERVATED NICHE MODULATES CANCER-ASSOCIATED PAIN: AN EMERGING THERAPEUTIC TARGET?
Provisionally accepted
- 1National Research Council (CNR), Roma, Italy
- 2IRCCS Istituto Nazionale Tumori Regina Elena, Rome, Italy
- 3Istituto Pasteur-Fondazione Cenci Bolognetti, Rome, Italy
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
ABSTRACT Crosstalk between cancer cells and the nervous system establishes the so-called "innervated niche". This component of the tumor microenvironment (TME) influences tumor progression and variably regulates the genesis and maintenance of cancer-related pain. Senescence is a cellular stress response emerging as a hallmark of cancer and aging. Through the inflammatory secretome referred to as senescence-associated secretory phenotype (SASP), senescent cells execute immunomodulation and tissue remodeling, participating in many physio-pathological processes. As inflammation is a key determinant of the TME as well as of neuropathies, in this review article we try to outline the possible role of senescence in the innervated niche. We argue that senescence can contribute to neuroinflammation, which is nowadays recognized as the initial factor triggering both cancer and non-cancer pain, by boosting local inflammation in the TME. At the same time, senescent cells can become targetable elements of the innervated niche to control cancer pain. We describe how the immune system supports the resolution of pain, and we suggest the possibility of harnessing natural killer (NK) cells, the prototype of innate immunity lymphocytes, for therapeutic approaches aimed at pain relief.
Keywords: Pain, Cancer, senescence, SASP, NK cell, Neuropathies, Neuroinflammation
Received: 28 Aug 2025; Accepted: 23 Oct 2025.
Copyright: © 2025 Antonangeli, Arcuri and Santoni. 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: Fabrizio Antonangeli, fabrizio.antonangeli@cnr.it
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.