Cancer immunotherapy–related adverse events: causes and challenges

Despite the success and ongoing promise of monoclonal antibody–targeted immune checkpoint inhibitor immunotherapy of advanced malignancies, in particular, antibodies directed against CTLA-4 and PD-1/PD-L1, the development of immune-related adverse events (irAEs) remains a constraint of this type of therapy. Although rarely fatal, the occurrence of irAEs may necessitate discontinuation of immunotherapy, as well as administration of corticosteroids or other immunosuppressive therapies that may not only compromise efficacy but also predispose for development of opportunistic infection. Clearly, retention of efficacy of immune checkpoint–targeted therapies with concurrent attenuation of immune-mediated toxicity represents a formidable challenge. In this context, the current brief review examines mechanistic relationships between these events, as well as recent insights into immunopathogenesis, and strategies which may contribute to resolving this issue. These sections are preceded by brief overviews of the discovery and functions of CTLA-4 and PD-1, as well as the chronology of the development of immunotherapeutic monoclonal antibodies which target these immune checkpoint inhibitors.Fil: Blidner, Ada Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Choi, Jennifer Ailen. Northwestern University; Estados UnidosFil: Cooksley, Tim. University of Manchester; Reino UnidoFil: Dougan, Michael. Harvard Medical School; Estados UnidosFil: Glezerman, Ilya. Memorial Sloan-kettering Cancer Center.; Estados UnidosFil: Ginex, Pamela. Oncology Nursing Society; Estados UnidosFil: Girotra, Monica. Weill Cornell Medicine; Estados Unidos. Memorial Sloan-kettering Cancer Center.; Estados UnidosFil: Gupta, Dipti. Memorial Sloan-kettering Cancer Center.; Estados UnidosFil: Johnson, Douglas. Vanderbilt University; Estados UnidosFil: Shannon, Vickie R.. University of Texas; Estados UnidosFil: Suarez Almazor, Maria. University of Texas; Estados UnidosFil: Rapoport, Bernardo L.. University of Pretoria; Sudáfrica. Medical Oncology Centre of Rosebank; SudáfricaFil: Anderson, Ronald. University of Pretoria; Sudáfric