Immunometabolic Reprogramming of Fibroblastic Reticular Cells in the Tumor Immune Microenvironment.

Area of Science:

• Immunology
• Metabolism
• Oncology

Background:

• Fibroblastic reticular cells (FRCs) are key stromal cells in lymphoid tissues and the tumor immune microenvironment (TIME).
• FRCs undergo significant metabolic changes that influence antitumor immune responses.
• Understanding FRC immunometabolism is crucial for developing effective cancer therapies.

Purpose of the Study:

• To review the immunometabolic reprogramming of FRCs in various cancer types.
• To highlight the roles of glucose, lipid, and amino acid metabolism in FRC function within the TIME.
• To explore how FRC metabolic alterations contribute to an immunosuppressive tumor microenvironment.

Main Methods:

• This is a narrative review synthesizing existing research.
• The review focuses on FRCs in lung cancer, breast cancer, gastric cancer, lymphoma, head and neck tumors, and melanoma.
• Key metabolic pathways discussed include glycolysis, fatty acid metabolism, and amino acid metabolism.

Main Results:

• Under conditions like hypoxia and inflammation, FRCs increase glycolysis and alter lipid metabolism.
• FRCs disrupt amino acid metabolism, leading to the secretion of immunosuppressive metabolites.
• These metabolic changes contribute to altered cytokine profiles and the formation of immune-supportive or suppressive niches.

Conclusions:

• FRC immunometabolic reprogramming is a significant factor in regulating antitumor immunity across diverse cancers.
• Cancer-specific metabolic alterations in FRCs create unique tumor microenvironments.
• Targeting FRC immunometabolism presents a promising avenue for novel cancer immunotherapies.