Reprogramming of glutamine metabolism and its impact on immune response in the tumor microenvironment.

Metabolic reprogramming and immune escape play a major role in tumorigenesis. Increasing number of studies have shown that reprogramming of glutamine metabolism is a putative determinant of the anti-tumor immune response in the tumor microenvironment (TME). Usually, the predatory uptake of glutamine by tumor cells in the TME results in the limited utilization of glutamine by immune cells and affects the anti-tumor immune response. The cell-programmed glutamine partitioning also affects the anti-tumor immune response. However, the reprogramming of glutamine metabolism in tumors modulates immune escape by regulating tumor PD-L1 expression. Likewise, the reprogramming of glutamine metabolism in the immune cells also affects their immune function. Additionally, different types of glutamine metabolism inhibitors extensively regulate the immune cells in the TME while suppressing tumor cell proliferation. Herein, we discuss how metabolic reprogramming of tumor and immune cells regulates anti-tumor immune responses, as well as functional changes in different immune cells in the context of targeting tumor glutamine metabolism, which can better explain the potential of targeting glutamine metabolism in combination with immunotherapy for cancer. Video abstract.

Diagnostic Performance of Dynamic Contrast-Enhanced MRI and 18F-FDG PET/CT for Evaluation of Soft Tissue Tumors and Correlation with Pathology Parameters.

RATIONALE AND OBJECTIVES: To assess the diagnostic performance of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and fluorine-18-fluorodeoxyglucose (18F-FDG) positron-emission tomography/computed tomography (PET/CT) parameters in evaluating the biological behavior of soft tissue tumors. MATERIALS AND METHODS: We retrospectively analyzed DCE-MRI and 18F-FDG PET/CT parameters in 78 patients with pathology-confirmed soft tissue tumors. A total of 78 patients had undergone DCE-MRI examination, while 24 patients with malignant soft tissue tumor had undergone 18F-FDG PET/CT examination. Microvessel density (MVD) and the Ki-67 labeling index (LI) were detected using immunohistochemistry. Differences in parameters (Ktrans, Kep, Ve, MVD, and Ki-67 LI) between benign and malignant tumors were compared. Differences in parameters (Ktrans, Kep, Ve, MVD, and SUVmax) between high- and low-proliferation malignant tumors (grouped by Ki-67 LI) were compared. Correlation of the DCE-MRI and 18F-FDG PET/CT parameters with MVD and Ki-67 LI was analyzed. RESULTS: Only the Ktrans, Kep, MVD, and Ki-67 LI differed significantly between the benign and malignant soft tissue tumors (all p < 0.001). Only Kep (p = 0.033) and SUVmax (p = 0.001) differed significantly between high- and low-proliferation malignant soft tissue tumors. Ktrans, Kep, and SUVmax correlated positively with MVD (r = 0.805, 0.778, 0.730, respectively; all p < 0.001), and with Ki-67 LI (r = 0.721, 0.685, 0.655, respectively; all p < 0.001). CONCLUSION: DCE-MRI and 18F-FDG PET/CT parameters indicate soft tissue tumor biological behavior and can be used to differentiate between benign and malignant soft tissue tumors and between high- and low-proliferation malignant soft tissue tumors.

Targeted Glucose or Glutamine Metabolic Therapy Combined With PD-1/PD-L1 Checkpoint Blockade Immunotherapy for the Treatment of Tumors - Mechanisms and Strategies.

Immunotherapy, especially PD-1/PD-L1 checkpoint blockade immunotherapy, has led tumor therapy into a new era. However, the vast majority of patients do not benefit from immunotherapy. One possible reason for this lack of response is that the association between tumors, immune cells and metabolic reprogramming in the tumor microenvironment affect tumor immune escape. Generally, the limited amount of metabolites in the tumor microenvironment leads to nutritional competition between tumors and immune cells. Metabolism regulates tumor cell expression of PD-L1, and the PD-1/PD-L1 immune checkpoint regulates the metabolism of tumor and T cells, which suggests that targeted tumor metabolism may have a synergistic therapeutic effect together with immunotherapy. However, the targeting of different metabolic pathways in different tumors may have different effects on tumor immune escape. Herein, we discuss the influence of glucose metabolism and glutamine metabolism on tumor immune escape and describe the theoretical basis for strategies targeting glucose or glutamine metabolism in combination with PD-1/PD-L1 checkpoint blockade immunotherapy.