4.7 Article

Dihydroartemisinin remodels macrophage into an M1 phenotype via ferroptosis-mediated DNA damage

Journal

FRONTIERS IN PHARMACOLOGY
Volume 13, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2022.949835

Keywords

tumor-associated macrophages (TAMs); dihydroartemisinin (DHA); ferroptosis; DNA damage; NF-kappa B

Funding

  1. Cultivating Project for Young Scholar at Hubei University of Medicine [2020QDJZR002, 2021QDJZR015, 2019QDJZR02]
  2. Innovative Research Program for Graduates of Hubei University of Medicine [YC2022027]
  3. Advantages Discipline Group (Medicine) Project in Higher Education of Hubei Province ( 2021-2025) [2022XKQY2]
  4. Precision Medicine Project of Taihe Hospital of Shiyan [2019JJXM007]
  5. National Training Program of Innovation and Entrepreneurship for Undergraduates [202213249001, 202210929001, S202210929004, S202210929007, S202210929010]
  6. Scientific and Technological Project of Sinopharm DongFeng General Hospital [2022S08]
  7. Foundation of Health Commission of Hubei Province [WJ2021f053]
  8. Science and Technology Research and Development Project of Shiyan [2021K70]

Ask authors/readers for more resources

This study demonstrates that Dihydroartemisinin (DHA) can remodel tumor-associated macrophages (TAMs) into an anti-tumor phenotype and induce ferroptosis and DNA damage response in TAMs. The study also shows that ferroptosis and DNA damage response in TAMs regulate the phenotypic remodeling induced by DHA. This provides a novel strategy and therapeutic target for anti-lung cancer immunotherapy.
Lung cancer recruits tumor-associated macrophages (TAMs) massively, whose predominantly pro-tumor M2 phenotype leads to immunosuppression. Dihydroartemisinin (DHA) has been proven to remodel TAM into an anti-tumor M1 phenotype at certain concentrations in the present study, which was hypothesized to facilitate anti-lung cancer immunotherapy. However, how DHA remodels the TAM phenotype has not yet been uncovered. Our previous work revealed that DHA could trigger ferroptosis in lung cancer cells, which may also be observed in TAM thereupon. Sequentially, in the current study, DHA was found to remodel TAM into the M1 phenotype in vitro and in vivo. Simultaneously, DHA was observed to trigger ferroptosis in TAM and cause the DNA damage response and NF-kappa B activation. Conversely, the DHA-induced DNA damage response and NF-kappa B activation in TAM were attenuated after the inhibition of ferroptosis in TAM using an inhibitor of ferroptosis. Importantly, a ferroptosis inhibitor could also abolish the DHA-induced phenotypic remodeling of TAM toward the M1 phenotype. In a nutshell, this work demonstrates that DHA-triggered ferroptosis of TAM results in DNA damage, which could activate downstream NF-kappa B to remodel TAM into an M1 phenotype, providing a novel strategy for anti-lung cancer immunotherapy. This study offers a novel strategy and theoretical basis for the use of traditional Chinese medicine monomers to regulate the anti-tumor immune response, as well as a new therapeutic target for TAM phenotype remodeling.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available