Sorting out the complexities of autoimmunity and checkpoint inhibitors: Not so easy
A partir d'une revue de la littérature publiée jusqu'en 2017 (49 articles, 123 patients), cette étude analyse le risque d'événements indésirables liés à l'utilisation d'inhibiteurs des points de contrôle immunitaire chez des patients atteints de cancer et d'une maladie auto-immune
Clinical use of checkpoint inhibitor (CPI) therapy for cancer has grown rapidly; there are currently 6 approved agents that are increasingly used for a broad array of tumors. These drugs seem to hold the potential for durable response rates in patients with advanced disease and are not classically immunosuppressive in the vein of traditional, nontargeted chemotherapeutic agents (1). Immunologically, CPIs target several ligands found largely on T cells. These ligands normally dampen ongoing T-cell responses and physiologically serve to protect the host under conditions of chronic antigen exposure in order to limit collateral damage during a chronic and ongoing immune response. Put simply, immunologic checkpoints are brakes on an activated immune system; CPIs remove or diminish these brakes and reinvigorate an exhausted immune response (2). With this reductionist model in mind, it is not hard to understand the myriad autoimmune and/or autoinflammatory complications associated with CPIs. These complications, known as immune-related adverse events (irAEs), have been described as a possible Achilles' heel of cancer immunotherapies in general (3).
Annals of Internal Medicine , éditorial, 2017