title: The Kynurenine Pathway Is a Double-Edged Sword in Immune-Privileged Sites and in Cancer: Implications for Immunotherapy.
abstract: The term "immune privilege" was originally coined to describe the suppression of inflammatory responses within organs protected by anatomic barriers, ie, the eyes, brain, placenta, and testes. However, cellular and metabolic processes, which orchestrate immune responses, also control inflammation within these sites. Our current understanding of tolerogenic mechanisms has extended the definition of immune privilege to include hair follicles, the colon, and cancer. By catabolizing tryptophan, cells expressing the enzyme indoleamine-2,3-dioxygenase produce kynurenine metabolites, which orchestrate local and systemic responses to control inflammation, thus maintaining immune privilege. This review highlights the double-edged role played by the kynurenine pathway (KP), which establishes and maintains immune-privileged sites while contributing to cancer immune escape. The identification of the underlying molecular drivers of the KP in immune-privileged sites and in cancer is essential for the development of novel therapies to treat autoimmunity and cancer and to improve transplantation outcomes.
authors: Chronic Viral Illness Service, McGill University Health Centre, Montreal, QC, Canada.; The Research Institute of the McGill University Health Centre, Montreal, QC, Canada.; Professor of Medicine, Division of Hematology, McGill University Health Centre, Montreal, QC, Canada.; Louis Lowenstein Chair in Hematology and Oncology, McGill University, Montreal, QC, Canada.
authors: Jean-Pierre
authors: JP
authors: Routy
authors: Postdoctoral Fellow, Gustave Roussy Cancer Campus, Villejuif, France.; INSERM U1015, Villejuif, France.
authors: Bertrand
authors: B
authors: Routy
authors: Research Associate, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
authors: Gina M
authors: GM
authors: Graziani
authors: Chronic Viral Illness Service, McGill University Health Centre, Montreal, QC, Canada.; Postdoctoral Fellow, The Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
authors: Vikram
authors: V
authors: Mehraj
keywords: HIV; IDO; cancer; immune-privileged sites; kynurenine pathway; tryptophan