Metabolism of Tryptophan, Glutamine, and Asparagine in Cancer Immunotherapy-Synergism or Mechanism of Resistance?

Abstract

Amino acids are crucial components of proteins, key molecules in cellular physiology and homeostasis. However, they are also involved in a variety of other mechanisms, such as energy homeostasis, nitrogen exchange, further synthesis of bioactive compounds, production of nucleotides, or activation of signaling pathways. Moreover, amino acids and their metabolites have immunoregulatory properties, significantly affecting the behavior of immune cells. Immunotherapy is one of the oncological treatment methods that improves cytotoxic properties of one's own immune system. Thus, enzymes catalyzing amino acid metabolism, together with metabolites themselves, can affect immune antitumor properties and responses to immunotherapy. In this review, we will discuss the involvement of tryptophan, glutamine, and asparagine metabolism in the behavior of immune cells targeted by immunotherapy and summarize results of the most recent investigations on the impact of amino acid metabolites on immunotherapy.