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Clinical and translational attributes of immune-related adverse events

Nature Cancer volume 5, pages 557–571 (2024)Cite this article

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Abstract

With immune checkpoint inhibitors (ICIs) becoming the mainstay of treatment for many cancers, managing their immune-related adverse events (irAEs) has become an important part of oncological care. This Review covers the clinical presentation of irAEs and crucial aspects of reversibility, fatality and long-term sequelae, with special attention to irAEs in specific patient populations, such as those with autoimmune diseases. In addition, the genetic basis of irAEs, along with cellular and humoral responses to ICI therapy, are discussed. Detrimental effects of empirically used high-dose steroids and second-line immunosuppression, including impaired ICI effectiveness, call for more tailored irAE-treatment strategies. We discuss open therapeutic challenges and propose potential avenues to accelerate personalized management strategies and optimize outcomes.

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Fig. 1: Factors contributing to the emergence and burden of irAEs.
Fig. 2: Spectrum and dynamics of irAEs.
Fig. 3: Immunological mechanisms of irAEs.

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Acknowledgements

All figures were created with https://www.biorender.com. Owing to space and reference limitations, we were unable to discuss and cite all interesting studies performed in this field.

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Author notes

  1. These authors contributed equally: Karijn P. M. Suijkerbuijk, Mick J. M. van Eijs.

Authors and Affiliations

  1. Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands

    Karijn P. M. Suijkerbuijk & Mick J. M. van Eijs

  2. Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands

    Mick J. M. van Eijs & Femke van Wijk

  3. University Medical Center Utrecht and Princess Máxima Center, Utrecht, the Netherlands

    Alexander M. M. Eggermont

  4. Comprehensive Cancer Center Munich of the Technical University of Munich and the Ludwig Maximilian University, Munich, Germany

    Alexander M. M. Eggermont

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Competing interests

K.P.M.S. has advisory relationships with Bristol Myers Squibb, Novartis, MSD, Pierre Fabre and AbbVie and has received honoraria from Novartis, MSD and Sairopa and research funding from BMS, Philips and TigaTx, all paid to the institution. F.v.W. has received advisory and/or speaker fees from Takeda and Johnson & Johnson and research funding from BMS, Takeda, Sanofi, Pfizer, Galapagos and Leo Pharma. A.M.M.E. has received honoraria for advisory relationships from Agenus, Boehringer Ingelheim, BioInvent, BioNTech, Brenus, CatalYm, Epics, GenOway, IO Biotech, IQVIA, ISA Pharmaceuticals, Merck & Co/MSD, Oncimmune, Pfizer, Pierre Fabre, Sairopa, Sellas, Scorpion, SkylineDX, TigaTx and Trained Therapeutics and moreover speaker fees from BMS and MSD and has equity in IO Biotech, Sairopa and SkylineDX. No potential conflicts of interest were disclosed by M.J.M.v.E.

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Suijkerbuijk, K.P.M., van Eijs, M.J.M., van Wijk, F. et al. Clinical and translational attributes of immune-related adverse events. Nat Cancer 5, 557–571 (2024). https://doi.org/10.1038/s43018-024-00730-3

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