Abstract
There has been significant progress in utilizing our immune system against cancer, mainly by checkpoint blockade and T cell-mediated therapies. The field of cancer immunotherapy is growing rapidly but durable clinical benefits occur only in a small subset of responding patients. It is currently recognized that cancer creates a suppressive metabolic microenvironment, which contributes to ineffective immune function. Metabolism is a common cellular feature, and although there has been significant progress in understanding the detrimental role of metabolic changes of the tumor microenvironment (TEM) in immune cells, there is still much to be learned regarding unique targetable pathways. Elucidation of cancer and immune cell metabolic profiles is critical for identifying mechanisms that regulate metabolic reprogramming within the TEM. Metabolic targets that mediate immunosuppression and are fundamental in sustaining tumor growth can be exploited therapeutically for the development of approaches to increase the efficacy of immunotherapies. Here, we will highlight the importance of metabolism on the function of tumor-associated immune cells and will address the role of key metabolic determinants that might be targets of therapeutic intervention for improvement of tumor immunotherapies.
Highlights
It is well-established that metabolic reprogramming is a hallmark of cancer progression [1,2,3]
Several immune cell types, such as macrophages, B cells, T cells, NK and NKT cells, neutrophils, dendritic cells (DCs), and myeloidderived suppressor cells (MDSCs), which are present in the tumor microenvironment (TME), have an active role in the process of cancer progression [5, 6]
The metabolic state of the TME is regulated by the metabolic activity of the cancer cell, which alters the availability of nutrients in the microenvironment as a result of metabolic competition between cancer and immune cells for key nutrients, such as glucose, glutamine, lipids, and amino acids [7,8,9]
Summary
Thibault Le Bourgeois1,2†, Laura Strauss, Halil-Ibrahim Aksoylar 1,2, Saeed Daneshmandi 3, Pankaj Seth 3, Nikolaos Patsoukis and Vassiliki A. There has been significant progress in utilizing our immune system against cancer, mainly by checkpoint blockade and T cell-mediated therapies. Metabolism is a common cellular feature, and there has been significant progress in understanding the detrimental role of metabolic changes of the tumor microenvironment (TEM) in immune cells, there is still much to be learned regarding unique targetable pathways. Elucidation of cancer and immune cell metabolic profiles is critical for identifying mechanisms that regulate metabolic reprogramming within the TEM. Metabolic targets that mediate immunosuppression and are fundamental in sustaining tumor growth can be exploited therapeutically for the development of approaches to increase the efficacy of immunotherapies. We will highlight the importance of metabolism on the function of tumor-associated immune cells and will address the role of key metabolic determinants that might be targets of therapeutic intervention for improvement of tumor immunotherapies.
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