New toxicity profile for novel immunotherapy agents: focus on immune-checkpoint inhibitors. (2nd January 2016)

• Record Type: Journal Article
• Authors: Ciccarese, C; Alfieri, S; Santoni, M; Santini, D; Brunelli, M; Bergamini, C; Licitra, L; Montironi, R; Tortora, G; Massari, F
• Is Part Of: Expert opinion on drug metabolism and toxicology. Volume 12:Number 1(2016:Jan.)
• Page Start: 57
• Page End: 75
• Publication Date: 2016-01-02
• Subjects: adverse events -- immune-checkpoint inhibitors -- immunotherapy -- safety profile -- toxicity; Drugs -- Toxicology -- Periodicals; Drugs -- Metabolism -- Periodicals; 615.7
• DOI: 10.1517/17425255.2016.1120287
• Languages: English
• ISSNs: 1742-5255

Abstract

Abstract : Introduction : Tumor development results from a cancer-induced immunosuppression (immune-editing). Immunotherapy has revolutionized the treatment paradigm for many malignancies, putting clinicians before novel toxicities, of immune-mediated etiology (immune-related adverse events). Areas covered : Immune-mediated toxicity depends on both innate and adaptive immunity mechanisms. Healthy tissue damage depends on an aspecific T-cell hyperactivation response causing cross-reaction with normal tissues, which leads to an overproduction of CD4 T-helper cell cytokines and an abnormal migration of cytolytic CD8 T-cells. By stimulating a diffuse T-cell repertoire expansion, immune-checkpoint inhibitors counteract tumor growth but reduce the self-tolerance, damaging healthy organs. In this review, we summarize the toxicity profile of the novel immune-checkpoint inhibitors and their clinical implications, we are convinced that a deep understanding and a prompt resolution of the paradigmatic toxicities of these drugs will result in clinical benefits to patients and an enhanced antitumor effect. Expert opinion : A focus on immunotoxicity is important in the education of clinicians and will improve patient safety. There is a willingness to tailor specific immune-therapies to each cancer patient, and to stimulate researchers through understanding of the physiopathogenesis, using the hypothesis that immune-mediated toxicities can be used as predictors of response or a prognostic sign of survival, thereby guiding therapeutic decisions.