Accepted for/Published in: JMIRx Bio
Date Submitted: Oct 14, 2025
Open Peer Review Period: Oct 20, 2025 - Dec 15, 2025
Date Accepted: Jan 11, 2026
(closed for review but you can still tweet)
Warning: This is an author submission that is not peer-reviewed or edited. Preprints - unless they show as "accepted" - should not be relied on to guide clinical practice or health-related behavior and should not be reported in news media as established information.
Second Breath: Systems-Level Model of Localized Immune Cascade Programming in Desmoplastic Tumors (In Silico-Validated, Literature-Anchored)
ABSTRACT
“Second Breath”, a testable conceptual framework for sequential, localized immune programming in desmoplastic solid tumors. Each cascade module is modeled in silico and explicitly cross-referenced to published in vitro and in vivo evidence (see References), supporting biological plausibility without claiming new wet-lab experiments in vitro. The framework specifies controlled, stepwise intratumoral activation of innate and adaptive immunity under limited systemic exposure. Network and enrichment analyses highlight coordinated hubs (e.g., TNF, TLR4, STAT1, CTLA4, CD274) and implicate β-catenin/Wnt-linked programs at trafficking and checkpoint-readiness steps, aligning with the proposed sequence logic. Collectively, “Second Breath” provides a mechanistic rationale and testable predictions, including predefined go/no-go criteria, for converting immune-cold, desmoplastic tumors into more responsive states and offers a structured basis for preclinical validation.
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