New toxicity profile for novel immunotherapy agents: Focus on immune-checkpoint inhibitors

C. Ciccarese, S. Alfieri, M. Santoni, D. Santini, M. Brunelli, C. Bergamini, L. Licitra, R. Montironi, G. Tortora, F. Massari

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)57-74
Number of pages18
JournalExpert Opinion on Drug Metabolism and Toxicology
Volume12
Issue number1
DOIs
Publication statusPublished - Jan 2 2016

Keywords

  • adverse events
  • immune-checkpoint inhibitors
  • immunotherapy
  • safety profile
  • toxicity

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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