The DOI matches its Crossref record; 64 of the 64 references it cites were found in a registry or an index.
Chloroquine modulates antitumor immune response by resetting tumor-associated macrophages toward M1 phenotype
Open accessAbstract
Resetting tumor-associated macrophages (TAMs) is a promising strategy to ameliorate the immunosuppressive tumor microenvironment and improve innate and adaptive antitumor immunity. Here we show that chloroquine (CQ), a proven anti-malarial drug, can function as an antitumor immune modulator that switches TAMs from M2 to tumor-killing M1 phenotype. Mechanistically, CQ increases macrophage lysosomal pH, causing Ca 2+ release via the lysosomal Ca 2+ channel mucolipin-1 (Mcoln1), which induces the activation of p38 and NF-κB, thus polarizing TAMs to M1 phenotype. In parallel, the released Ca 2+ activates transcription factor EB (TFEB), which reprograms the metabolism of TAMs from oxidative phosphorylation to glycolysis. As a result, CQ-reset macrophages ameliorate tumor immune microenvironment by decreasing immunosuppressive infiltration of myeloid-derived suppressor cells and Treg cells, thus enhancing antitumor T-cell immunity. These data illuminate a previously unrecognized antitumor mechanism of CQ, suggesting a potential new macrophage-based tumor immunotherapeutic modality.
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The Use of Alternative Strategies for Enhanced Nanoparticle Delivery to Solid Tumors
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Metadata
- Authors
- Chen, D., Xie, J., Fiskesund, R., Dong, W., Liang, X., Lv, J., Jin, X., Liu, J., Mo, S., Zhang, T., Cheng, F., Zhou, Y., Zhang, H., Tang, K., Ma, J., Liu, Y., & Huang, B.
- Venue
- Nature Communications
- Published
- 2018-02-28
- Volume
- 9
- Issue
- 1
- Pages
- 873-873
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2802078831
- Cited by
- 489
- References
- 64
- FWCI
- 15.70
- Type
- journal article
- Language
- en
- Open access
- gold
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- Chen, D., Xie, J., Fiskesund, R., Dong, W., Liang, X., Lv, J., Jin, X., Liu, J., Mo, S., Zhang, T., Cheng, F., Zhou, Y., Zhang, H., Tang, K., Ma, J., Liu, Y., & Huang, B. (2018). Chloroquine modulates antitumor immune response by resetting tumor-associated macrophages toward M1 phenotype. Nature Communications. https://doi.org/10.1038/s41467-018-03225-9
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