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

Sahil Inamdar Abhirami P Suresh Joslyn L Mangal Nathan D Ng Alison Sundem Hoda Shokrollahzadeh Behbahani Thomas E Rubino Jordan R Yaron Taravat Khodaei Matthew Green Marion Curtis Abhinav P Acharya

Biomaterials

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:

Published: October 2023

Succinate is a substance that helps control how immune and cancer cells behave in tumors.
Researchers found that using special tiny particles called PES microparticles can deliver succinate directly to tumors and change how immune cells (like macrophages) act.
In tests, using these PES microparticles with a cancer drug reduced tumor size significantly and helped the body create a stronger immune response against cancer.

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 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.

Download full-text PDF	Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10544711	PMC
http://dx.doi.org/10.1016/j.biomaterials.2023.122292	DOI Listing

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