Tumors, tumor therapies, autoimmunity and the eye

Area of Science:

• Ophthalmology
• Immunology
• Oncology

Background:

• The eye is an immune-privileged site, typically protected from autoimmune attacks.
• Autoimmune uveitis is rare, but cancer-associated retinopathy (CAR) involves eye destruction via autoantibodies against tumor-expressed ocular antigens.
• Emerging cancer therapies can paradoxically induce autoimmunity in immune-privileged organs.

Purpose of the Study:

• To examine how novel cancer therapies, including immune checkpoint inhibitors and MEK/BRAF inhibitors, can lead to autoimmune eye diseases.
• To understand the mechanisms by which these therapies affect retinal cells and trigger autoimmune responses.

Main Methods:

• Review of current literature on cancer therapies and their ocular side effects.
• Analysis of mechanisms involving immune checkpoints and small molecule inhibitors (MEK/BRAF) in relation to ocular autoimmunity.
• Examination of ectopic antigen expression by tumors and subsequent autoimmune reactions.

Main Results:

• Immune checkpoint inhibitors can enhance anti-tumor responses but also induce autoimmune diseases, including in the eye.
• MEK/BRAF inhibitors, while targeting tumor signaling, exhibit toxicity to non-dividing retinal cells.
• Both therapeutic classes can render retinal cells targets of autoimmune destruction, leading to conditions like CAR.

Conclusions:

• Modern cancer treatments pose a risk of inducing autoimmune eye diseases, even in immune-privileged ocular environments.
• Understanding these off-target effects is crucial for managing patients undergoing these advanced cancer therapies.
• Further research is needed to mitigate the ocular toxicity associated with these promising anti-cancer treatments.