Awakening antitumour immunity in the multimorbid host: a hypothesis coupling cryoablation-induced immunogenic cell death with multi-target Traditional Chinese Medicine

Abstract

Most patients with cancer are older adults living with several other chronic illnesses, and both the tumour and its commonest companions—cardiometabolic disease, type 2 diabetes and depression—are sustained by a shared, immunosuppressive inflammatory milieu. In this setting many tumours are immunologically “cold”: poorly infiltrated by cytotoxic T and natural killer (NK) cells, enriched for regulatory T cells (Tregs) and M2 macrophages, and embedded in a chronically inflamed “soil” that also drives the comorbidities. Here we advance a mechanistic hypothesis: that two low-harm modalities applied together can reawaken antitumour immunity in this host while sparing the physiological reserve that radical treatment consumes. Minimally invasive cryoablation destroys tumour in situ and releases tumour antigens together with damage-associated molecular patterns (calreticulin, ATP, HMGB1), driving immunogenic cell death, dendritic-cell maturation and CD8+ T-cell priming; multi-target Traditional Chinese Medicine (TCM) acts on the same inflammatory substrate—dampening NF-κB, IL-6 and TNF-α signalling, lowering lactate, and reducing regulatory-T-cell and M2 dominance—to remodel the tumour microenvironment. We propose that their convergence turns a “cold” microenvironment “hot” and, because the targeted substrate is shared, yields a one-to-many benefit that extends from the tumour to its inflammatory comorbidities. We situate this hypothesis within the three-stage Tumour Green Therapy framework—Dominant Control ( bà dào , 霸道), Supportive Integration ( wáng dào , 王道) and Harmonisation and Maintenance ( dì dào , 帝道)—which sequences local immunogenic debulking, systemic immune support and microenvironmental harmonisation according to tumour urgency and host constitution, and maps TCM syndrome patterns onto measurable immune and inflammatory readouts (neutrophil-to-lymphocyte ratio, CRP, IL-6/TNF-α) that could serve as biomarkers. We define the immunological phenotype of this host, specify which patients should and should not receive the approach, remain candid about its limitations—herb–drug interactions, product quality and the scarcity of randomised data—and pre-specify both a two-stage prospective test and the observations that would refute each element of the hypothesis. Its central, falsifiable claim is that cryoablation plus multi-target TCM reawakens antitumour immunity and reduces total treatment burden, including polypharmacy, without compromising survival or quality of life.