Essakhi Nora, Bertucci Alexandre, Baeza-Kallee Nathalie, Colin Carole, Lavignolle-Heguy Rosario, Garcia-Gonzalez Paulina, Argüello Rafael J, Tchoghandjian Aurélie, Tabouret Emeline
Aix-Marseille Univ, CNRS, INP, Inst Neurophysiopathol, GlioME Team, Marseille, France.
APHM, CHU Timone, Service de Neurooncologie, Marseille, France.
Front Immunol. 2024 Dec 23;15:1431112. doi: 10.3389/fimmu.2024.1431112. eCollection 2024.
In recent decades, immunometabolism in cancers has emerged as an interesting target for treatment development. Indeed, the tumor microenvironment (TME) unique characteristics such as hypoxia and limitation of nutrients availability lead to a switch in metabolic pathways in both tumor and TME cells in order to support their adaptation and grow. Glioblastoma (GBM), the most frequent and aggressive primary brain tumor in adults, has been extensively studied in multiple aspects regarding its immune population, but research focused on immunometabolism remains limited. Here, we provide an overview of immunometabolism adaptation of myeloid cells in cancers with a specific focus on GBM and other brain tumors, before describing current therapeutic strategies targeting metabolic pathways. The main myeloid cells composing the GBM TME include tumor-associated macrophages (TAMs), which comprise both peripheral macrophages and local microglia, as well as myeloid-derived suppressor cells. The metabolic pathways involved in myeloid cell remodeling encompass the tricarboxylic acid cycle (TCA cycle), the lipid, glucose and amino acid metabolism and hypoxia. Developing treatments that target these metabolic pathways in tumor growth and its TME is a promising and increasing field. It includes both drug-repurposing and the development of innovative metabolic therapies. We finally provide an overview of all clinical trials in neuro-oncology involving treatments modifying cell metabolism and provide the preclinical rationale for both drugs already evaluated within clinical trials and potential candidates for future trials.
近几十年来,癌症中的免疫代谢已成为治疗开发的一个有趣靶点。事实上,肿瘤微环境(TME)的独特特征,如缺氧和营养物质供应受限,导致肿瘤细胞和TME细胞中的代谢途径发生转变,以支持它们的适应和生长。胶质母细胞瘤(GBM)是成人中最常见、侵袭性最强的原发性脑肿瘤,在其免疫群体的多个方面都得到了广泛研究,但专注于免疫代谢的研究仍然有限。在这里,我们概述了癌症中髓系细胞的免疫代谢适应情况,特别关注GBM和其他脑肿瘤,然后描述了目前针对代谢途径的治疗策略。构成GBM TME的主要髓系细胞包括肿瘤相关巨噬细胞(TAM),它包括外周巨噬细胞和局部小胶质细胞,以及髓系来源的抑制细胞。参与髓系细胞重塑的代谢途径包括三羧酸循环(TCA循环)、脂质、葡萄糖和氨基酸代谢以及缺氧。开发针对肿瘤生长及其TME中这些代谢途径的治疗方法是一个有前景且不断发展的领域。这包括药物重新利用和创新代谢疗法的开发。我们最后概述了神经肿瘤学中所有涉及改变细胞代谢治疗的临床试验,并为已在临床试验中评估的药物以及未来试验的潜在候选药物提供临床前依据。
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