Abstract
Tumor-infiltrating myeloid cells are a prominent pro-tumorigenic immune cell population that limit host anti-tumor immunity and present a significant obstacle for many cancer immunotherapies. Targeting the mechanisms regulating myeloid cell function within the tumor microenvironment may overcome immunotherapy resistance in some cancers. Recent discoveries in the emerging field of immunometabolism reveal that the metabolic profiles of intratumoral myeloid cells are rewired to adapt to the nutrition-limited tumor microenvironment, and this shapes their pro-tumor phenotypes. Interestingly, metabolic modulation can shift these myeloid cells toward the immune-stimulating anti-tumor phenotype. In this review, we will highlight the roles of specific metabolic pathways in the activation and function of myeloid cells, and discuss the therapeutic value of metabolically reprogramming myeloid cells to augment and improve outcomes with cancer immunotherapy.
Highlights
The tumor microenvironment (TME) is often infiltrated by a large number of myeloid cells, which represent a prominent immune component in tumors and play a critical role in modulating antitumor immunity (De Vlaeminck et al, 2016)
Due to their immunosuppressive features, the accumulation of myeloid-derived suppressor cells (MDSCs) correlates with accelerated tumor progression, immune escape, and resistance to immunotherapy, which leads to poor clinical outcomes (Li et al, 2021)
The mammalian target of rapamycin pathway induces the expression of glycolysis-related enzymes including HK1, hexokinase-2 (HK2), phosphofructokinase-1 (PFK1), pyruvate kinase M2 (PKM2), and lactate dehydrogenase (LDH), which are vital for Monocytic MDSCs (M-MDSCs) lineage commitment (Uehara et al, 2019)
Summary
Reviewed by: Chiara Porta, University of Eastern Piedmont, Italy Narendra Verma, NYU Grossman School of Medicine, United States. Targeting Metabolic Pathways of Myeloid Cells Improves Cancer Immunotherapy. Tumor-infiltrating myeloid cells are a prominent pro-tumorigenic immune cell population that limit host anti-tumor immunity and present a significant obstacle for many cancer immunotherapies. Targeting the mechanisms regulating myeloid cell function within the tumor microenvironment may overcome immunotherapy resistance in some cancers. Recent discoveries in the emerging field of immunometabolism reveal that the metabolic profiles of intratumoral myeloid cells are rewired to adapt to the nutrition-limited tumor microenvironment, and this shapes their pro-tumor phenotypes. Metabolic modulation can shift these myeloid cells toward the immune-stimulating anti-tumor phenotype. We will highlight the roles of specific metabolic pathways in the activation and function of myeloid cells, and discuss the therapeutic value of metabolically reprogramming myeloid cells to augment and improve outcomes with cancer immunotherapy
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