DQIS — Distributed Quorum-Based Independent Immune Surveillance (formerly: Quantum-Inspired): A Theoretical Framework for Multi-Channel Independent Immune Surveillance

DQIS — Distributed Quorum-Based Independent Immune Surveillance. Consolidated Framework (v36, current cleaned version — June 2026). A theoretical / in-silico framework for oncological immune surveillance. The core idea — borrowed from Byzantine Fault Tolerance in distributed computing — is that a set of statistically independent verification channels, aggregated by a k-of-N quorum rule, reduces the joint probability of tumour immune escape multiplicatively rather than additively. The panel is carried by distinct engineered T-cell variants; detection is a distributed consensus, not a single receptor decision. Empirical foundations. The channel layer is now stated as a panel of six engineered sensing channels in two categories: five "presence" channels (mHSP70 membrane HSP70/Gb3 · PS phosphatidylserine · CSFT cell-surface redox/thiols · T-δ chromosomal-instability sensor via cGAS-STING · T-α metabolic/Warburg) plus one "absence" channel (NK/missing-self, detecting loss of MHC-I — the only literature-proven anti-correlated escape axis; Kärre & Ljunggren, Nature 1986; human tissue Wessel, JITC 2024). Channels are readers of surface/secreted proxies, not internal-state sensors; security is expressed as a measured ROC, not as a product of assumed error probabilities. Inter-channel independence is measured, not assumed: within-tumour Kendall τ-b on real single-cell RNA-seq — melanoma (GSE72056), GBM (GSE131928), PDAC (GSE155698), cross-validated on GSE115978 — gives all pairwise τ < 0.20 (ρ ≈ 0.08), with an effective number of independent channels N_eff ≈ 3.3–4.1 of 5. Direct θ measurements: GBM θ = 0.199 (7,911 cells) — reclassified from cold to hot; PDAC θ = 1.214 (11,448 EPCAM+ cells) — confirmed intrinsically cold; normal pancreas θ = 1.107 (GSE84133, Baron 2016) — already high before any cancer, which is why θ alone cannot discriminate PDAC and motivates the population-level penetrance signal. The per-channel error probability p_i for the engineered panel remains the single open empirical ("Level-B") variable. Operative efficacy claims. All figures are stratified by tumour type and stated as illustrative, with assumptions made explicit. With six independent channels at a quorum k = 2 and a conservative ~10% per-channel evasion probability, the probability a tumour evades the panel is ≈ 0.005% (caught > 99.99%); at the engineering target (~1%/channel) it falls below 10⁻⁷%. In canonical fold-reduction terms relative to the natural system: ~75× at the Phase 0 operating point (range 30–75×, lower bound at p_i = 0.01), ~857× at k = 2 (idealised), and ~5,000–30,000× for the established multi-channel panel (the high-multiplier estimate, target-conditional on p_i ≈ 0.01). The ~4,000,000× figure (k = 5 unanimous, θ = 0) is a theoretical ceiling only, non-operative, preserved for completeness. The anti-correlated NK/missing-self channel and the Double Memory Imprint make these values upper bounds on escape. Key architectural developments. (1) Channel redesign and measurement (June 2026): the original five biophysical channels were reduced to a measured, essentiality-anchored panel — T-δ recast as a CIN/cGAS-STING sensor (orthogonal to the metabolic axis), T-γ* (bioelectric) dropped as not trans-cellularly readable, T-β (mechanical) and T-ε (topological) retained only as non-core AND-gate/vote candidates; the five-channel material is fully superseded and consolidated to a single citation. (2) NK/missing-self "absence" channel added, built on the iCAR inhibitory-receptor primitive (Fedorov 2013), paired with the Double Memory Imprint as its temporal partner. (3) Adaptive quorum tier k = 1/N + Gate_G (Ki-67 proliferation AND-gate) — security from biological specificity rather than statistical rarity; requires resolution of O29 (Ki-67 nanobody, Phase 2+) and is the single most critical post-Phase 0 investment. (4) Population-level modules that require no new channels or construct changes: the IPS penetrance signal (15.5× in PDAC) for biophysically-cold tumours, the Pattern Drift Sensor for early evolutionary-resistance interception, and the Pulsed Activity Architecture. Immunoediting (O39) is addressed on three legs — a multi-channel quorum, the essentiality brake (~10⁹×; three of six channels are essential hallmarks the cell cannot silence without a fitness cost, with μ anchored to the measured human single-gene inactivation rate ≈ 10⁻⁶, Araten 2005), and the DMI/PDS temporal layer — and was empirically stress-tested on real escape: two Merkel-cell-carcinoma patients relapsing via MHC-I loss (Paulson 2018) and a genetically-defined CD19+/CD19− B-ALL escape (GSE153697), where channels did not co-fall and independence held (N_eff ≈ 4.65/6). Self-audit. The companion Objections Register (v35, 39 mapped objections) is published as a live adversarial audit: roughly 13 resolved/addressed, 9 rendered moot by the current panel, 4 low, 7 medium, and 5 high-severity open, with O34 (the "Channel Paradox") reclassified as a design principle. The high-severity open items are the honest limits of a theoretical framework — O7 (clonal-haematopoiesis drift over decades), O8 (progressive epigenetic silencing of transgenes), O14 (paediatric validation), O27 (standalone non-genotoxic conditioning still combined with genotoxic agents in all current trials), O38 (passive sensing of internal state is physically closed — the reframe to surface/secreted proxies). Two structural objections were re-evaluated with a laboratory-excluded logic (status reflects what could be demonstrated with the means available — computation on real data — with wet-lab confirmation noted separately): O2 (channel independence) is now RESOLVED-measured, and O39 (immunoediting) is STRUCTURAL-addressed with co-resistance measured. The companion Addendum I (v20) provides the Clayton-copula tail-dependence formalism, the IPS derivation, TASE recalibration, and the Adaptive Quorum integration into the formal threat model. Origin and intent. This framework was developed by an independent researcher without academic affiliation, using AI-assisted conceptual exploration and formalisation (AI as a formal interlocutor, not a co-author). It is explicitly theoretical: no wet-lab validation has been performed. The Phase 0 Proof-of-Concept — T-δ (CIN) + a second retained proxy (T-α or mHSP70), k = 1/2, melanoma preclinical model, €2–5M, 24–30 months — is the single required experimental investment for framework credibility; Gate_G resolution (O29) is the recommended second. The document is offered as a foundation for academic discussion and a target for experimental falsification, not as a claim of completeness or as clinical guidance. Terminological note. From v22.0, DQIS expands as "Distributed Quorum-Based Independent Immune Surveillance." The architecture uses Byzantine Fault Tolerance k-of-N quorum logic over the six-channel panel. T-δ v2.0 is a Chromosomal Instability sensor (cGAS-STING pathway), mechanistically orthogonal to the metabolic channels; the legacy epigenetic/methylation reader and the bioelectric T-γ* channel are superseded and retained only in the Superseded Ledger and prior Zenodo versions. Canonical terminology: T-α … T-ε plus NK/missing-self, "quorum k-of-N", "orthogonal biophysical/surface-proxy channels", Byzantine Fault Tolerance. Contact: [email protected] documents (current versions): Scientific Objections Register v35; Addendum I — Temporal Stratification of Tail Dependence Risk v20. Released under CC BY 4.0. Contact: [email protected] Related documents: - Register of Scientific Objections v35.0: https://zenodo.org/records/21128725 - Addendum I — Temporal Stratification of Tail Dependence Risk v20: https://zenodo.org/records/21128894