Acupuncture in remodeling the tumor microenvironment: current status and challenges

The tumor microenvironment (TME) is a dynamic ecosystem in which malignant, immune, stromal, and vascular compartments continuously interact, and plays a key role in tumor initiation, development and treatment resistance. In recent years, acupuncture, as an ancient neuromodulatory intervention means of traditional medicine, has shown promise in supportive oncology by attenuating chemotherapy- and radiotherapy-induced toxicities, modulating immunity, and improving quality-of-life metrics. Yet, a mechanistic framework that links acupuncture to TME reprogramming remains to be established. From the perspective of TME, we reviews the latest research status of acupuncture anti-tumor mechanism. Evidence synthesized indicates that acupuncture (i) triggers apoptosis of malignant cells, (ii) re-educates innate (NK, macrophage, dendritic, and mast) and adaptive (T and B lymphocyte) immune subsets, and (iii) normalizes tumor vasculature, so as to inhibit tumor growth and metastasis, synergize chemotherapy and immunotherapy, and promote physical rehabilitation. We further outline opportunities and challenges for translating acupuncture into evidence-based oncology. Using breast cancer as a paradigm, we emphasize the need to evaluate the role of acupuncture in different molecular subtypes and within integrative survivorship care. Furthermore, we aim to link its benefit of relieving symptoms with TME modulation mechanisms, thereby constructing an integrated evidence chain connecting "clinical symptoms-acupuncture intervention-TME modulation-long-term prognosis.". Interdisciplinary trials that couple mechanistic TME readouts with robust clinical endpoints are now warranted to definitively establish the efficacy and safety of acupuncture in cancer care.