琥珀酸是一个重要的代谢物，在肿瘤微环境（TME）中调节免疫细胞和癌细胞的代谢。在本文中，我们报告了聚乙烯琥珀酸（PES）微粒（MPs）生物材料介导的琥珀酸在TME中的控制释放对巨噬细胞反应的调节。在具有临床相关的BRAFV600E突变型YUMM1.1黑色素瘤的免疫缺陷老龄小鼠中，局部给予PES MPs，无论是否与BRAF抑制剂全身给药，肿瘤体积都减小了三倍。TME中的PES MPs还导致M1型巨噬细胞的维持，并上调TSLP和1型干扰素途径。令人印象深刻的是，这导致了TME中促炎性适应性免疫应答的生成，表现为T辅助细胞1型和T辅助细胞17型细胞的增加。总体而言，我们在这一具有挑战性的肿瘤模型中得出的结果表明，免疫代谢重塑的PES MP策略为开发强大的癌症免疫治疗提供了一种途径。版权所有©2023年Elsevier Ltd. 保留所有权利。

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 BRAFV600E 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.Copyright © 2023 Elsevier Ltd. All rights reserved.