Succinate in the tumor microenvironment affects tumor growth and modulates tumor associated macrophages.

Autor: Inamdar S; Chemical Engineering, School for the Engineering of Matter, Transport, and Energy, Arizona State University, Tempe, AZ, 85281, USA., Suresh AP; Biological Design, School for the Engineering of Matter, Transport, and Energy, Arizona State University, Tempe, AZ, 85281, USA., Mangal JL; Biological Design, School for the Engineering of Matter, Transport, and Energy, Arizona State University, Tempe, AZ, 85281, USA., Ng ND; Molecular Biosciences and Biotechnology, The College of Liberal Arts and Sciences, Arizona State University, Tempe, AZ, 85281, USA., Sundem A; Chemical Engineering, School for the Engineering of Matter, Transport, and Energy, Arizona State University, Tempe, AZ, 85281, USA., Behbahani HS; Chemical Engineering, School for the Engineering of Matter, Transport, and Energy, Arizona State University, Tempe, AZ, 85281, USA., Rubino TE Jr; Department of Immunology, Mayo Clinic, Scottsdale, AZ, 85259, USA; Department of Cancer Biology, Mayo Clinic, Scottsdale, AZ, 85259, USA., Yaron JR; Biological Design, School for the Engineering of Matter, Transport, and Energy, Arizona State University, Tempe, AZ, 85281, USA., Khodaei T; Biomedical Engineering, School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, 85281, USA., Green M; Chemical Engineering, School for the Engineering of Matter, Transport, and Energy, Arizona State University, Tempe, AZ, 85281, USA; Materials Science and Engineering, School for the Engineering of Matter, Transport, And Energy, Arizona State University, Tempe, AZ, 85281, USA., Curtis M; Department of Immunology, Mayo Clinic, Scottsdale, AZ, 85259, USA; Department of Cancer Biology, Mayo Clinic, Scottsdale, AZ, 85259, USA; College of Medicine and Science, Mayo Clinic, Scottsdale, AZ, 85259, USA., Acharya AP; Chemical Engineering, School for the Engineering of Matter, Transport, and Energy, Arizona State University, Tempe, AZ, 85281, USA; Biological Design, School for the Engineering of Matter, Transport, and Energy, Arizona State University, Tempe, AZ, 85281, USA; Biomedical Engineering, School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, 85281, USA; Materials Science and Engineering, School for the Engineering of Matter, Transport, And Energy, Arizona State University, Tempe, AZ, 85281, USA; Biodesign Center for Immunotherapy, Vaccines and Virotherapy, Arizona State University, Tempe, AZ, 85281, USA; Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, United States. Electronic address: abhi.acharya@asu.edu.
Jazyk: angličtina
Zdroj: Biomaterials [Biomaterials] 2023 Oct; Vol. 301, pp. 122292. Date of Electronic Publication: 2023 Aug 26.
DOI: 10.1016/j.biomaterials.2023.122292
Abstrakt: 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 V600E 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.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Abhinav P. Acharya reports was provided by National Institutes of Health. Abhinav P. Acharya reports was provided by National Science Foundation. Abhinav P. Acharya has patent pending to Arizona State University.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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