Stocking the toolbox—Using preclinical models to understand the development and treatment of immune checkpoint inhibitor‐induced immune‐related adverse events

Abstract

SummaryCancer patients treated with immune checkpoint inhibitors (ICIs) are susceptible to a broad and variable array of immune‐related adverse events (irAEs). With increasing clinical use of ICIs, defining the mechanism for irAE development is more critical than ever. However, it currently remains challenging to predict when these irAEs occur and which organ may be affected, and for many of the more severe irAEs, inaccessibility to the tissue site hampers mechanistic insight. This lack of understanding of irAE development in the clinical setting emphasizes the need for greater use of preclinical models that allow for improved prediction of biomarkers for ICI‐initiated irAEs or that validate treatment options that inhibit irAEs without hampering the anti‐tumor immune response. Here, we discuss the utility of preclinical models, ranging from exploring databases to in vivo animal models, focusing on where they are most useful and where they could be improved.

The evolving landscape of immune‐related adverse events that follow immune checkpoint immunotherapy in cancer patients

“…For the last manuscript of this section, Morgan Cina, Jessica Venegas, and Arabella Young put together a very comprehensive review on the preclinical models available that capture some aspects of the irAE etiology across different organ systems. These can be used to study the biological underpinnings of irAEs, along with their relationship to anti‐tumor immune responses 55 . They examine the contexts for which these models are most useful, how they could be improved, as well as the advantages and disadvantages of different model systems.…”

“…These can be used to study the biological underpinnings of irAEs, along with their relationship to anti-tumor immune responses. 55 The ability to predict the occurrence of specific irAEs to ICI will be a critical step towards the development of prophylactic therapies and could prove valuable in making informed decisions regarding tailoring cancer treatment options for each patient.…”