Journal Article

Targeting Tumor Metabolism: A New Challenge to Improve Immunotherapy

Ben Ayed, Farhat, Benammar Elgaaied, Amel, Kouidhi, Soumaya

2018

Overview

Currently, a marked number of clinical trials on cancer treatment have revealed the success of immunomodulatory therapies based on immune checkpoint inhibitors that activate tumor-specific T cells. However, the therapeutic efficacy of cancer immunotherapies is only restricted to a small fraction of patients. A deeper understanding of key mechanisms generating an immunosuppressive tumor microenvironment (TME) remains a major challenge for more effective antitumor immunity. There is a growing evidence that the TME supports inappropriate metabolic reprogramming that dampens T cell function, and therefore impacts the antitumor immune response and tumor progression. Notably, the immunosuppressive TME is characterized by a lack of crucial carbon sources critical for T cell function and increased inhibitory signals. Here, we summarize the basics of intrinsic and extrinsic metabolic remodeling and metabolic checkpoints underlying the competition between cancer and infiltrating immune cells for nutrients and metabolites. Intriguingly, the upregulation of tumor programmed death-L1 and cytotoxic T lymphocyte-associated antigen 4 alters the metabolic programme of T cells and drives their exhaustion. In this context, targeting both tumor and T cell metabolism can beneficially enhance or temper immunity in an inhospitable microenvironment and markedly improve the success of immunotherapies.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Amino acids / Animals / Antibodies, Monoclonal - therapeutic use / Antigens / Antigens, Neoplasm - immunology / Antitumor activity / Apoptosis / Biosynthesis / Cancer immunotherapy / Cancer therapies / Carbon sources / Cells / Cellular Reprogramming / Clinical outcomes / Clinical trials / Competition / Costimulatory and Inhibitory T-Cell Receptors - immunology / Cytotoxicity / Dehydrogenases / Enzymes / Glucose / Humans / Hypoxia / Immune checkpoint inhibitors / immune checkpoints / Immunity / Immunity (Disease) / Immunization / Immunology / Immunomodulation / Immunotherapy / Immunotherapy - methods / Kinases / Lymphocytes / Lymphocytes T / metabolic checkpoints / Metabolism / Metabolites / Metastasis / Neoplasms - immunology / Neoplasms - metabolism / Neoplasms - therapy / Nutrients / Physical fitness / T-lymphocyte metabolism / T-Lymphocytes - immunology / T-Lymphocytes - transplantation / Transcription factors / tumor cell metabolism / Tumor Escape / Tumor Microenvironment / Tumors