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Review
. 2024 Jul 29;24(1):312.
doi: 10.1186/s12886-024-03575-7.

Cytokines in PD-1 immune checkpoint inhibitor adverse events and implications for the treatment of uveitis

Aaron C Brown  1   2 , José Quiroz  1   2 , Devayu A Parikh  1   2 , Yafeng Li  3 , Lukas Ritzer  2 , Richard Rosen  1   4 , Avnish Deobhakta  5   6
Affiliations
Review

Cytokines in PD-1 immune checkpoint inhibitor adverse events and implications for the treatment of uveitis

Aaron C Brown et al. BMC Ophthalmol. .

Abstract

Immune checkpoint inhibitors (ICI) such as Programmed cell Death 1 (PD-1) inhibitors have improved cancer treatment by enhancing the immune system's ability to target malignant cells. Their use is associated with immune-related adverse events (irAEs), including uveitis. The profile of pro-inflammatory cytokines underlying Anti-PD-1-induced uveitis shares significant overlap with that of non-infectious uveitis. Current corticosteroid treatments for uveitis while effective are fraught with vision threatening side effects. The cytokine profile in ICI-related uveitis has a large overlap with that of noninfectious uveitis, this overlap strongly supports the potential for therapy that activates the PD-1 axis in the eye to treat uveitis. Indeed, ICI related uveitis often resolves with cessation of the ICI, restoring the endogenous PD-1 axis. The potential benefit of targeting many pro-inflammatory cytokines via local PD-1 axis activation is mitigating ocular inflammation while minimizing adverse effects.

Keywords: Drug Therapy; Immune Checkpoint Inhibitors; Uveitis.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
The PD-1 receptor-ligand interaction prevents T Cell activation. ICI prevent this interaction which leads to activation of T Cells. Original Image
Fig. 2
Fig. 2
The cytokines associated with immune-related adverse events (irAEs) vary significantly depending on the specific type of cancer being treated. This Venn diagram illustrates the distinct cytokine profiles observed across different cancer types in response to Anti-PD-1 Immune Checkpoint Inhibitors. The limited overlap between cytokine signatures underscores the unique immunological landscapes associated with each cancer
Fig. 3
Fig. 3
PD-1 blockade, through the use of PD-1 or PD-L1 mAbs, can trigger immune related adverse events (irAEs) through the release of proinflammatory cytokines (a). In the eye, elevation of this set of cytokines presents as intraocular inflammation (b) Inflammation secondary to cytokine release is treated with targeted therapy, typically with reduction of a single cytokine (c)
Fig. 4
Fig. 4
The cytokine profiles elevated in Non-Infectious Uveitis and Anti-PD-1 irAE Uveitis demonstrate a notable degree of overlap
Fig. 5
Fig. 5
PD-1 blockade, through the use of PD-1 or PD-L1 mAbs, can trigger immune related adverse events (irAEs) through the release of proinflammatory cytokines (a). In the eye, elevation of this set of cytokines presents as intraocular inflammation (b), with anterior, intermediate, posterior uveitis or any combination thereof. Intravitreal delivery of PD-1 agonist (c) could restore the PD-1 axis with a return of cytokines to homeostatic levels. With the abatement of inflammatory signaling, uveitis could in turn resolve (d)
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