Dihydroartemisinin as a pharmacokinetically constrained immune-conditioning pulse in cancer therapy
- 1Department of Immunology, Zhuhai Campus of Zunyi Medical University
- 2Shengli Clinical Medical College of Fujian Medical University
- 3Department of Thoracic Surgery, Affiliated Hospital of Zunyi Medical University
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.
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BibTeX
@article{wei2026dihydroartemisinin,
title = {{Dihydroartemisinin as a pharmacokinetically constrained immune-conditioning pulse in cancer therapy}},
author = {Pei Wei and Jiahua Wang and Yuan Cao and Yongxiang Song and Zhiyong Wang},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1955672},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1955672/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Dihydroartemisinin as a pharmacokinetically constrained immune-conditioning pulse in cancer therapy
AU - Pei Wei
AU - Jiahua Wang
AU - Yuan Cao
AU - Yongxiang Song
AU - Zhiyong Wang
PY - 2026
DA - 2026/10/29
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1955672
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1955672/full
AB - 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.
SN - 1664-3224
ER -