{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T06:19:17Z","timestamp":1787552357066,"version":"build-2736575974"},"reference-count":132,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Most patients with cancer are older adults living with several other chronic illnesses, and both the tumour and its commonest companions\u2014cardiometabolic disease, type 2 diabetes and depression\u2014are sustained by a shared, immunosuppressive inflammatory milieu. In this setting many tumours are immunologically \u201ccold\u201d: 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 \u201csoil\u201d 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\n                    <jats:italic>in situ<\/jats:italic>\n                    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\u2014dampening NF-\u03baB, IL-6 and TNF-\u03b1 signalling, lowering lactate, and reducing regulatory-T-cell and M2 dominance\u2014to remodel the tumour microenvironment. We propose that their convergence turns a \u201ccold\u201d microenvironment \u201chot\u201d 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\u2014Dominant Control (\n                    <jats:italic>b\u00e0 d\u00e0o<\/jats:italic>\n                    , \u9738\u9053), Supportive Integration (\n                    <jats:italic>w\u00e1ng d\u00e0o<\/jats:italic>\n                    , \u738b\u9053) and Harmonisation and Maintenance (\n                    <jats:italic>d\u00ec d\u00e0o<\/jats:italic>\n                    , \u5e1d\u9053)\u2014which 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-\u03b1) 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\u2014herb\u2013drug interactions, product quality and the scarcity of randomised data\u2014and 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.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1904534","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T05:28:18Z","timestamp":1787549298000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Awakening antitumour immunity in the multimorbid host: a hypothesis coupling cryoablation-induced immunogenic cell death with multi-target Traditional Chinese Medicine"],"prefix":"10.3389","volume":"17","author":[{"given":"Lihui","family":"Liu","sequence":"first","affiliation":[{"name":"School of Traditional Chinese Medicine, Hubei University of Chinese Medicine","place":["Wuhan, Hubei, China"]},{"name":"Department of Oncology, Hubei Provincial Hospital of Traditional 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