Dihydroartemisinin as a pharmacokinetically constrained immune-conditioning pulse in cancer therapy
Year: 2026
Type: article
Abstract: Mechanistic assignment in cancer immunology often assumes that durable antitumor effects reflect sustained pharmacologic pressure on tumor cells. Dihydroartemisinin (DHA) provides a useful test case for revisiting this assumption because clinically achievable systemic exposure is brief and free-drug availability is constrained by substantial protein binding. We therefore propose that brief systemic DHA exposure may act as a pharmacokinetically constrained immune-conditioning pulse whose durable antitumor effects, when present, could involve persistent tumor-intrinsic injury, immune relay, or both. Within this framework, transient tumor or stromal stress may be converted into longer-lived antitumor activity through myeloid-state transition, dendritic-cell activation, relief of immune exclusion, and subsequent CD8 + T-cell priming. Current evidence does not yet establish a dominant immune mechanism under exposure-matched conditions. Suppressive myeloid-state change, a tumor stress–dendritic cell–CD8 + T-cell axis, and direct lymphocyte responsiveness are competing hypotheses for exposure-matched testing alongside direct tumor-cell effects. This framework informs exposure-matched experimental design, biomarker development, and rational immunotherapy combinations, and provides a falsifiable prioritization scheme based on exposure matching, temporal precedence, persistence after washout, and in vivo necessity.
Source: Frontiers in Immunology
Institutions: Zunyi Medical University, Fujian Medical University
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7224466082