Macrophages as central mediators of perineural invasion in cancer: Implications for pain and prognosis.

Authors

Shiji Cheng, Yuze Hua, Quan Liao, Qiaofei Liu

Published in

Biochimica et biophysica acta. Reviews on cancer. Pages 189687. Aug 16, 2026. Epub Aug 16, 2026.

Abstract

Perineural invasion (PNI) is associated with tumor progression, therapeutic resistance, and poor prognosis. However, the mechanisms driving tumor-nerve interactions remain incompletely understood. Emerging evidence suggests that macrophages function as key regulators within the perineural niche by linking inflammation, neural remodeling, extracellular matrix reorganization, and immunometabolic signaling. This review proposes a macrophage-centered framework for understanding PNI progression and summarizes macrophage-mediated mechanisms involved in nerve invasion, perineural homeostasis disruption, and tumor-nerve crosstalk. We further discuss recent advances in macrophage-targeted therapeutic strategies and highlight current challenges, including limited direct evidence and barriers to clinical translation. Understanding macrophage-mediated PNI may provide new insights into therapeutic interventions targeting the neural-tumor-immune microenvironment.

PMID:
42604706
Bibliographic data and abstract were imported from PubMed on 17 Aug 2026.

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