Immune-checkpoint inhibitors (ICIs), including anti-cytotoxic T lymphocyte antigen 4 (CTL A-4), anti-programmed cell death 1 (PD-1) and anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are arguably the most important development in cancer therapy over the past decade. The indications for these agents continue to expand across malignancies and disease settings, thus reshaping many of the previous standard-of-care approaches and bringing new hope to patients. One of the costs of these advances is the emergence of a new spectrum of immune-related adverse events (irAEs), which are often distinctly different from the classical chemotherapy-related toxicities. Owing to the growing use of ICIs in oncology, clinicians will increasingly be confronted with common but also rare irAEs; hence, awareness needs to be raised regarding the clinical presentation, diagnosis and management of these toxicities. In this Review, we provide an overview of the various types of irAEs that have emerged to date. We discuss the epidemiology of these events and their kinetics, risk factors, subtypes and pathophysiology, as well as new insights regarding screening and surveillance strategies. We also highlight the most important aspects of the management of irAEs.

Inflammatory bowel diseases (IBD) can be broadly divided into Crohn's disease (CD) and ulcerative colitis (UC) from their clinical phenotypes. Over 150 host susceptibility genes have been described, although most overlap between CD, UC and their subtypes, and they do not adequately account for the overall incidence or the highly variable severity of disease. Replicating key findings between two long-term IBD cohorts we have defined distinct networks of taxa associations within intestinal biopsies of CD and UC patients. Disturbances in an association network containing taxa of the Lachnospiraceae and Ruminococcaceae families, typically producing short chain fatty acids, characterize frequently relapsing disease and poor responses to treatment with anti-TNF-α therapeutic antibodies. Alterations of taxa within this network also characterize risk of later disease recurrence of patients in remission after the active inflamed segment of CD has been surgically removed.

In an analysis of a large cohort of subjects with IBD, we found a significant association between symptoms of depression or anxiety and clinical recurrence. Patients with IBD should therefore be screened for clinically relevant levels of depression and anxiety and referred to psychologists or psychiatrists for further evaluation and treatment.

Immune-checkpoint inhibitors (ICIs) are reshaping the prognosis of many cancer types and are progressively becoming a standard of care for many of them. Cancer immunotherapy has started a revolution in the oncology therapeutic landscape, bringing new hope to patients but also a whole new spectrum of toxicities for practitioners to manage. Oncologists and specialists involved in the pluridisciplinary management of immune-related adverse events (irAEs) are increasingly confronted with the therapeutic challenge of severe and/or refractory cases. In this personal view, we summarize the therapeutic strategies reported to manage them. Based on current knowledge of irAE pathogenesis and our immunological expertise, we also transpose the use of new biologic and non-biologic immunosuppressive agents, used to treat primary autoimmune disorders (AIDs), in the context of severe and/or steroid refractory irAE management. Depending on the immune-type predominant infiltrate, we propose a personalized treatment algorithm beyond corticosteroids. A shut-off strategy, intended to treat severe or steroid-refractory irAEs, based on the efficient inhibition of key inflammatory components involved in their pathophysiological processes, and limit potential adverse effects of drug immunosuppression on tumor response is proposed. This approach goes beyond current guidelines, challenging the step-by-step increase in drug immunosuppression proposed so far.