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Review
. 2023 Sep;318(1):89-95.
doi: 10.1111/imr.13238. Epub 2023 Jul 8.

Role of B cells in immune-related adverse events following checkpoint blockade

Kavita M Dhodapkar  1   2 , Alyssa Duffy  1 , Madhav V Dhodapkar  2   3
Affiliations
Review

Role of B cells in immune-related adverse events following checkpoint blockade

Kavita M Dhodapkar et al. Immunol Rev. 2023 Sep.

Abstract

Blockade of immune checkpoints has transformed the therapy of several cancers. However, immune-related adverse events (irAEs) have emerged as a major challenge limiting the clinical application of this approach. B cells are recognized as major players in the pathogenesis of human autoimmunity and have been successfully targeted to treat these disorders. While T cells have been extensively studied as therapeutic targets of immune checkpoint blockade (ICB), these checkpoints also impact B cell tolerance. Blockade of immune checkpoints in the clinic is associated with distinct changes in the B cell compartment that correlate with the development of irAEs. In this review, we focus on the possible role of humoral immunity, specifically human B cell subsets and autoantibodies in the pathogenesis of ICB-induced irAEs. There remains an unmet need to better understand the T:B cell cross talk underlying the activation of pathogenic B cells and the development of ICB-induced irAEs. Such studies may identify new targets or approaches to prevent or treat irAEs and improve the application of ICB therapy in cancer.

Keywords: B cells; adverse events; autoimmunity; cancer; immune checkpoint blockade; mechanism.

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Conflict of interest statement

Conflicts of interest: The authors have declared that no conflict of interest exists.

Figures

Figure 1.
Figure 1.. Role for B cells and T:B cross-talk in immune-related adverse events (irAEs) following immune-checkpoint blockade.
Activation of autoreactive B cells as well as T cells following checkpoint blockade contributes to irAEs. Baseline levels of CD4 cells as well as changes in CD21loT-bet+ B cells have been linked to the development of high-grade irAEs. Cross-talk between these cells may contribute to tissue inflammation in autoimmune tissues. Highlighted boxes represent some potential areas of intervention for preventing these irAEs.
See this image and copyright information in PMC

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