Caloric Restriction as an Adjunct in Parasite-Associated Cancers: Convergent Mechanisms and a Proposed Trial Framework

Parasite-associated cancers — including Opisthorchis viverrini-associated cholangiocarcinoma (CCA), Schistosoma haematobium-associated bladder squamous cell carcinoma (SCC), Strongyloides stercoralis/HTLV-1-associated adult T-cell leukaemia/lymphoma (ATL), and Plasmodium falciparum-associated endemic Burkitt lymphoma (eBL) — share a common immune microenvironment feature: Th2/regulatory T cell (Treg) polarisation that suppresses CD8+ cytotoxic T lymphocyte (CTL) activity and attenuates immune checkpoint inhibitor (ICI) response. A December 2025 Nature Metabolism study demonstrated that dietary restriction reprograms CD8+ T cells through ketone body oxidation (ketolysis), reversing exhaustion and enhancing ICI efficacy — the precise immune defect this programme identified in helminth-associated cancers. Separately, fasting-induced mTOR suppression disrupts a key parasite survival pathway: intracellular parasites including Toxoplasma gondii and Leishmania spp. exploit PI3K/Akt/mTOR signalling to suppress autophagy-mediated clearance, and mTOR inhibition restores parasite killing in preclinical models. This hypothesis paper distinguishes two fasting strategies with different...