Succinate in the tumor microenvironment affects tumor growth and modulates tumor associated macrophages.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 37643489.
- Also identified by DOI 10.1016/j.biomaterials.2023.122292 and PMC identifier 10544711.
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Abstract
Succinate is an important metabolite that modulates metabolism of immune cells and cancer cells in the tumor microenvironment (TME). Herein, we report that polyethylene succinate (PES) microparticles (MPs) biomaterial mediated controlled delivery of succinate in the TME modulates macrophage responses. Administering PES MPs locally with or without a BRAF inhibitor systemically in an immune-defective aging mice with clinically relevant BRAF<sup>V600E</sup> mutated YUMM1.1 melanoma decreased tumor volume three-fold. PES MPs in the TME also led to maintenance of M1 macrophages with up-regulation of TSLP and type 1 interferon pathway. Impressively, this led to generation of pro-inflammatory adaptive immune responses in the form of increased T helper type 1 and T helper type 17 cells in the TME. Overall, our findings from this challenging tumor model suggest that immunometabolism-modifying PES MP strategies provide an approach for developing robust cancer immunotherapies.
Medical subject headings
- Succinic Acid
- Melanoma