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Ciccarese, C; Alfieri, S; Santoni, M; Santini, D; Brunelli, M; Bergamini, C; Licitra, L; Montironi, R; Tortora, G; Massari, F
Expert opinion on drug metabolism & toxicology, 01/2016, Letnik: 12, Številka: 1Journal Article
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.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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