Beyond survival: psychoneuroimmunology-driven cancer psychological rehabilitation—a paradigm shift from symptom management to biobehavioral remodeling

Cancer treatment paradigms have evolved from solely focusing on tumor eradication to optimizing survivorship trajectories. However, current psychological rehabilitation approaches predominantly target symptom relief, such as anxiety, depression, and fatigue, without direct evidence of influencing cancer’s biological processes like recurrence, metastasis, or immune evasion. This review, grounded in psychoneuroimmunology, advocates for elevating psychological rehabilitation from an auxiliary support role to a synergistic component of antitumor therapy. Central to this perspective is redefining rehabilitation endpoints to include immune reconstitution indices and tumor dormancy maintenance capacity. We propose a dynamic “stress-inflammation-immune escape” cycle model and emphasize the development of precision psychological interventions tailored to tumor genetic mutation profiles and associated psychological phenotypes. The article synthesizes three strands of recent evidence: First, clinical translational findings suggesting that psychological interventions may be accompanied by shifts in immunological indices such as the regulatory T cell (Treg)/T helper 17 (Th17) ratio and may correlate with the efficacy of PD-1 inhibitors, although the available evidence rests largely on small samples and surrogate endpoints and is insufficient to establish causality; Second, mechanistic findings, derived predominantly from preclinical models, indicating that the brain-bone marrow axis may mediate epigenetic reprogramming of hematopoietic stem cells, the human relevance of which remains to be confirmed; and finally, technological developments such as digital phenotyping that offer exploratory directions for monitoring relapse and psychological deterioration, whose diagnostic performance has not yet been established in prospective studies. By advancing the interdisciplinary field of precision psychoimmuno-oncology, this review aims to establish a low-cost, high-benefit “brain-body combined therapy” paradigm, offering cancer survivors innovative strategies for comprehensive recovery beyond mere symptom control. Importantly, the hypothesis framework proposed herein rests predominantly on surrogate endpoints and preclinical evidence. Until hard endpoints from prospective randomized controlled trials become available, any effect of psychological interventions on tumor biological behavior should be regarded as a scientific hypothesis awaiting verification rather than an established clinical conclusion.