Abstract
BackgroundA close metabolic interaction between cancer and immune cells in the tumor microenvironment (TME) plays a pivotal role in cancer immunity. Herein, we have comprehensively investigated the glucose metabolic features of the TME at the single-cell level to discover feasible metabolic targets for the tumor immune status.MethodsWe examined expression levels of glucose transporters (GLUTs) in various cancer types using The Cancer Genome Atlas (TCGA) data and single-cell RNA-seq (scRNA-seq) datasets of human cancer tissues including melanoma, head and neck, and breast cancer. In addition, scRNA-seq data of immune cells in the TME acquired from human melanoma after immune checkpoint inhibitors were analyzed to investigate the dynamics of glucose metabolic profiles of specific immune cells.ResultsPan-cancer bulk RNA-seq showed that the GLUT3-to-GLUT1 ratio was positively associated with immune cell enrichment score. The scRNA-seq datasets of various human cancer tissues showed that GLUT1 was highly expressed in cancer cells, while GLUT3 was highly expressed in immune cells in TME. The scRNA-seq data obtained from human melanoma tissues pre- and post-immunotherapy showed that glucose metabolism features of myeloid cells, particularly including GLUTs expression, markedly differed according to treatment response.ConclusionsDifferently expressed GLUTs in TME suggest that GLUT could be a good candidate a surrogate of tumor immune metabolic profiles and a target for adjunctive treatments for immunotherapy.
Highlights
Dysfunction of the immune system in the tumor microenvironment (TME) plays a crucial role in cancer progression
The expression levels of GLUT1 and GLUT3, which are the main transporters for glucose uptake in cancer cells [24], were compared across different types of cancers using The Cancer Genome Atlas (TCGA) data
According to a previous study on lung cancer, GLUT3 is relatively highly expressed in immune cells within the TME, while GLUT1 is highly expressed in most cancer cells [13]
Summary
Dysfunction of the immune system in the tumor microenvironment (TME) plays a crucial role in cancer progression. Interaction of various cells in the TME with cancer cells causes immune suppression and/or exhaustion to induce cancer cellular progression [1, 2]. The close interaction of tumor immune and metabolic profiles provides an opportunity to target the metabolism of the TME to enhance the efficacy of cancer immunotherapy and develop a diagnostic and prognostic biomarker for evaluating metabolic immune functionality [7]. A close metabolic interaction between cancer and immune cells in the tumor microenvironment (TME) plays a pivotal role in cancer immunity. We have comprehensively investigated the glucose metabolic features of the TME at the single-cell level to discover feasible metabolic targets for the tumor immune status
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