Immunometabolism of Innate Immune Cells in Gastrointestinal Cancer

Cancer cells are often described as voracious consumers of nutrients, with glucose frequently cited as a key energy source; however, their metabolic plasticity allows them to adapt and utilize various substrates, including lipids and amino acids, to sustain growth and survival. However, the metabolic demands of immune cells within the tumor microenvironment (TME) are less commonly discussed despite their critical role in shaping the immune response. In this review, we explored the intricate interplay between immunometabolism and innate immunity cells in gastrointestinal cancers. We focused on how metabolic pathways, including glycolysis, fatty acid oxidation, and amino acid metabolism, drive the immunosuppressive functions of myeloid-derived suppressor cells (MDSCs) and tumor-associated neutrophils (TANs), tumor-associated macrophages (TAMs) and innate lymphocyte subsets such as NK cells. These cells contribute to a hostile immune landscape, supporting tumor growth and evasion from immune surveillance in a phenomenon of tumor-derived immunosuppression. Additionally, we investigated the influence of dietary interventions on the metabolic reprogramming of these immune cells, highlighting how nutrition can modulate the TME. Finally, we discussed emerging therapeutic strategies that target metabolic vulnerabilities in MDSCs, TANs, NK cells, and monocytes, offering a novel avenue for enhancing antitumor immunity. By dissecting these mechanisms, we aim to provide insights into how metabolic pathways can be harnessed to improve cancer treatment outcomes. This review underscores the importance of understanding immunometabolism not only as a driver of immune suppression but also as a potential therapeutic target in gastrointestinal cancer.