Commentary: Metabolism Impact on Immunotherapy

Over the years we have come to realize that the altered metabolic state of tumors can be influenced by the metabolic landscape of the tumor microenvironment. This collective metabolic state also affects the metabolism and the functioning of immune cells. We now appreciate that the process of metabolic reprogramming in cancers is complex, driven by mutations and/or epigenetic alterations and modified by the cellular context.⁽¹⁾ Glycolytic shifts and a concurrent reduction in oxidative phosphorylation enable cancer cells to adapt to changes in the tumor microenvironment and also affect tumor-associated immune cells such as macrophages, T cells, and myeloid-derived suppressor cells. It is also recognized that metabolic reprogramming confers metabolic liabilities, which can be exploited for the therapeutic targeting for cancer therapy.^(2,3) However, to capitalize on these advances to improve cancer immunotherapy, we need to understand more fully how metabolic pathways can influence the expression of biomarkers and immunotherapeutic targets on cancer cells and tissues.⁽⁴⁾ Immune cells detect and eliminate cancer cells, but under conditions of metabolic alterations, these cells fail to function effectively, resulting in tumor growth and failure of cancer immune therapies. The potential regulation, up or down, for example, programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1), can impact the use of checkpoint inhibitors. It is also of interest as to how metabolism affects lymphocyte differentiation into specific effector subsets⁽⁵⁾ and how the immune system is affected by the altered metabolic landscape of the tumor microenvironment.⁽⁶⁾ Immunosuppressive microenvironments induced by regulatory T cells present a major barrier to successful antitumor immunotherapy. Defining the suppressive mechanisms used by different types of tumor-infiltrating cells and influenced by metabolism is essential for the development of novel strategies for cancer treatment and positive clinical outcomes.⁽⁷⁾

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy is initiating a section dedicated to this topic that draws attention to the underlying similarities, differences, and functional consequences of metabolic pathways utilized by activated immune cells and cancer cells as it relates to immunotherapy. It is the intent of this section to highlight and, therefore, foster research that would lend to improvement of immunotherapy strategies and approaches. Areas of interest in the form of original research articles, review articles, minireviews, rapid communications, brief reports, perspectives, and commentary include, but are not limited to the following.