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Expert Opin Drug Metab Toxicol. 2016;12(1):57-75. doi: 10.1517/17425255.2016.1120287. Epub 2015 Dec 8.

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

Author information

1
a Medical Oncology , Azienda Ospedaliera Universitaria Integrata, University of Verona , Verona 37124 , Italy.
2
b SSD Oncologia medica Tumori Testa e Collo , Fondazione IRCCS - Istituto Nazionale dei Tumori , Milano 20133 , Italy.
3
c Clinica di Oncologia Medica, AOU "Ospedali Riuniti" , Polytechnic University of the Marche Region , Ancona 60126 , Italy.
4
d Department of Medical Oncology , Campus Bio-Medico University , Oncologia Medica, Rome , Italy.
5
e Department of Pathology and Diagnostic , Azienda Ospedaliera Universitaria Integrata, University of Verona , Verona 37124 , Italy.
6
f Section of Pathological Anatomy, School of Medicine, AOU Ospedali Riuniti , Polytechnic University of the Marche Region , Ancona 60126 , Italy.

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.

KEYWORDS:

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

PMID:
26565919
DOI:
10.1517/17425255.2016.1120287
[Indexed for MEDLINE]

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