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Moving towards personalized treatments of immune-related adverse events

Abstract

The enhancement of immune responses upon treatment with immune checkpoint inhibitors can have the desired outcome of reinvigorating antitumour immune surveillance, but often at the expense of immune-related adverse events (irAEs). This novel disease entity often prompts comparisons with, and extrapolation of treatment approaches from, primary autoimmune disorders. Accordingly, current treatment guidelines for irAEs make generic recommendations adapted from the literature describing primary autoimmune diseases, without taking into consideration the substantial disparity of the immunohistopathological findings within each organ affected by an irAE. The treatment modalities themselves are complex and have many potential drawbacks, such as serious and rarely fatal infections, drug toxicities overlapping with irAEs and the risk of compromising cancer immune surveillance. Herein, we provide an overview of key cellular and soluble immunological factors mediating irAEs and propose a model integrating this knowledge with the immunohistopathological findings of the affected organs for a personalized decision-making process for each patient.

Key points

  • Immune-related adverse events (irAEs) are occasionally serious, and rarely fatal, complications derived from treatment with immune checkpoint inhibitors (ICIs).

  • irAEs can result from either a breach of self-tolerance resulting in the production of autoreactive lymphocytes and autoantibodies, or a non-specific autoinflammatory reaction.

  • Corticosteroids remain the cornerstone of the treatment of irAEs; however, biological immunomodulatory agents are often needed in patients with severe reactions or reactions affecting vital organs.

  • We propose a personalized immunohistopathologically guided process for choosing the appropriate treatment regimen beyond first-line corticosteroids.

  • Immunomodulatory treatments can have organ-specific toxicities overlapping with the sites affected by irAEs; they can also be associated with an increased risk of serious infections and possible blunting of effects from ICIs.

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Fig. 1: Proposed immunopathogenic mechanisms for immune-related adverse events.
Fig. 2: Most commonly observed histopathological findings by affected organ systems.
Fig. 3: Proposed personalized treatment algorithm for the management of immune-related adverse events.

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K.E. and L.C. discussed the contents of this Review. K.E. performed the literature searches. All the authors contributed equally to the writing of the manuscript.

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Correspondence to Khashayar Esfahani.

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Esfahani, K., Elkrief, A., Calabrese, C. et al. Moving towards personalized treatments of immune-related adverse events. Nat Rev Clin Oncol 17, 504–515 (2020). https://doi.org/10.1038/s41571-020-0352-8

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