Deciphering metabolic reprogramming of immune cells within the tumor microenvironment.

backgroundImmunometabolic adaptations may induce tumor immune escape and immunotherapeutic resistance, representing crucial mechanisms in cancer progression. Understanding the metabolic rewiring of tumor-infiltrating immune cells as tumors advance could enhance current immune-oncology treatments.

methodsIn this study, we investigated metabolic heterogeneity in immune cells within both tumor and adjacent normal tissue using single-cell transcriptome profiling of colon cancer. We also utilized the MC38 colorectal cancer model, a commonly employed mouse tumor model, to assess the metabolic atlas of major immune cell populations in tumor and normal tissue.

resultsWe examined the immunometabolic features in tumor tissue and adjacent normal tissue using public single-cell transcriptomic datasets of colorectal cancer (CRC) patients, in which myeloid cells showed dominant metabolic activity. Using a mouse tumor model, we demonstrated distinct metabolic reprogramming of major immune cell types in tumor compared to normal tissue. Specifically, we observed increased glucose and lipid uptake, along with abundant lipid accumulation in tumor-infiltrating myeloid cells, particularly macrophages. Additionally, we identified diverse mitochondrial fitness and oxidative stress levels within the tumor immune microenvironment. Macrophages exhibited metabolic fitness, CD8

conclusionOverall, our study unveils the heterogeneity and dynamics of metabolic properties in immune cells within the tumor microenvironment. These findings provide insights for developing therapeutic strategies that target metabolism to enhance antitumor immunity.