{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T12:28:56Z","timestamp":1786624136344,"version":"build-2736575974"},"reference-count":94,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Three convergent phenomena in biomedical research have lacked a unified mechanistic explanation: the dendritic cell dysfunction of aging, the immune evasion of cancer, and the tolerogenic bias of chronic infection. Each is characterized by failure of type 1 conventional dendritic cell (cDC1) instruction and loss of its bioactive IL-12p70 output.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Hypothesis<\/jats:title>\n                    <jats:p>We propose that these three phenomena share a single molecular cause: sustained silencing of IRF8 by a four-step chain. SASP cytokines activate STAT3 in hematopoietic progenitors; STAT3 recruits DNMT1 and EZH2 to the IRF8 locus; dual DNA and histone methylation installs a bistable silencing state with no stable intermediate; IL-12 transcription and cDC1 instruction collapse. Each step is individually established in the literature. Their assembly is a deduction rather than a new discovery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Proposed correction<\/jats:title>\n                    <jats:p>A cDC1 manufactured ex vivo outside the SASP-STAT3 field, the \u03b1-type-1 polarized dendritic cell (\u03b1-DC1), is not subject to the chain and produces IL-12p70 at supraphysiological concentrations. If the chain is correct, \u03b1-DC1 administration should restore endogenous IRF8 expression, re-enable cDC1 surveillance, and decelerate biological aging as measured by DunedinPACE. We outline the mechanism, testable predictions, and falsification criteria.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1861044","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T05:38:37Z","timestamp":1785476317000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A proposed convergent molecular chain linking senescence, cancer, and chronic infection to a correctable failure of dendritic cell instruction"],"prefix":"10.3389","volume":"17","author":[{"given":"Andrew","family":"Caravello","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine, Rowan-Virtua School of Osteopathic Medicine","place":["Stratford, NJ, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Blidy","sequence":"additional","affiliation":[{"name":"SaltusBiotech","place":["Pleasanton, CA, United 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