Mechanistic Review — Parasite-Associated Cancers as Predicted Checkpoint Inhibitor Responders

Mechanistic review in the Hidden Infections research series. Parasite-associated cancers may be superior checkpoint inhibitor (ICI) responders compared to histologically matched cancers from helminth-naive populations, because chronic parasitic infection simultaneously elevates two positive predictors of ICI response: PD-L1 expression (via Th2/STAT6 upregulation) and tumour mutational burden (via genotoxin-driven somatic mutations). This review documents: the TOPAZ-1 Asia subgroup HR of 0.72 (versus global HR 0.80 for durvalumab in biliary tract cancer) as a signal consistent with helminth prevalence as an ICI response modifier; EBV-positive NHL checkpoint inhibitor data showing 47% ORR; and the complete absence of helminth serology from any of 200 ICI trials (Study 11). The central claim is methodological: we cannot determine whether helminth status modifies ICI response because no trial has ever measured it. Evidence tier: MODERATE (mechanistic hypothesis); EXPLORATORY (ICI response). CC0 public domain. AI-assisted draft pre-print.