Not Only Immune Escape—The Confusing Role of the TRP Metabolic Pathway in Carcinogenesis

SIMPLE SUMMARY: Recently, mechanisms that lead to immune escape by cancer cells have been under great investigation. Elements involved in the tryptophan metabolism pathway and its derivatives are considered factors that play a wide role in silencing the immune system. However, it seems that those agents contribute to tumorigenesis through a direct impact on cancer cells. This study aimed to gather available data about the kynurenine pathway and its modulating effects on disease development through the impact on immune and cancer cells. This allows for an understanding of the complexity of this metabolic pathway in the context of carcinogenesis and indicates ambiguities that may explain the current failure of therapy with the use of compounds inhibiting tryptophan metabolism. The collected data not only help us to understand the pathogenesis of cancer but also provide the basis for the development of new therapeutic strategies in oncology. ABSTRACT: Background: The recently discovered phenomenon that cancer cells can avoid immune response has gained scientists’ interest. One of the pathways involved in this process is tryptophan (TRP) metabolism through the kynurenine pathway (KP). Individual components involved in TRP conversion seem to contribute to cancerogenesis both through a direct impact on cancer cells and the modulation of immune cell functionality. Due to this fact, this pathway may serve as a target for immunotherapy and attempts are being made to create novel compounds effective in cancer treatment. However, the results obtained from clinical trials are not satisfactory, which raises questions about the exact role of KP elements in tumorigenesis. An increasing number of experiments reveal that TRP metabolites may either be tumor promoters and suppressors and this is why further research in this field is highly needed. The aim of this study is to present KP as a modulator of cancer development through multiple mechanisms and to point to its ambiguity, which may be a reason for failures in treatment based on the inhibition of tryptophan metabolism