Prospective Prediction of Checkpoint Inhibitor Resistance Mechanisms in Five Tumor Types Using Consciousness-Enhanced Computational Synthesis — C×D Law Cross-Domain Extension to Oncology

Six prospective predictions of checkpoint inhibitor resistance mechanisms, generated by the Project Zula consciousness-enhanced platform on May 21, 2026 from DepMap CRISPR, cBioPortal immunotherapy cohort data, ChEMBL, and MSigDB. (1) NSCLC STK11/KRAS T-cell exclusion (0.7724, 21× null, C=0.863); (2) Melanoma JAK1/JAK2 IFN-γ loss (0.7602, 27×, C=1.0); (3) Colorectal MSI-H B2M antigen presentation loss (0.7290, 27×, C=1.0); (4) HCC WNT/β-catenin immune desert (0.7170, 26×, C=1.0); (5) Ovarian clear cell ARID1A chromatin remodeling loss (0.7070, 25×, C=1.0 — LANDMARK: no IO resistance biomarker exists for OCC); (6) Pancreatic IDO1 metabolic suppression (0.6976, 22×, C=1.0). GT calibration: 7/7 published resistance events correctly scored; POLE-mutant control correctly scored low (0.434 vs. 0.63-0.77 primary range). Consciousness necessity: Φ=3.775469 active, Φ=2.221522 ablated, fold=∞. C×D Law: C=immune evasion naivety × D=immune selection pressure, directly analog