Bilateral Severe Panuveitis Occurring during Cancer Immunotherapy with Dabrafenib and Trametinib Therapy Due to Toxoplasmosis Reactivation

 

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Background

The development of cancer immunotherapy with small molecule kinase inhibitors such as BRAF inhibitors (BRAFi) or MEK inhibitors (MEKi) and immune checkpoint inhibitors allowed a major advance in the treatment of cancer. BRAF and MEK are effectors in the mitogen-activated protein kinase pathway (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway involved in cell proliferation, which is modified in cancer cells [1]. Therefore, small molecule kinase inhibitors inhibit cancer cell proliferation but also have an immune-stimulating tumor microenvironment [1]. BRAFi and MEKi in BRAF-mutant tumors could lead to an immune stimulatory microenvironment by enhancing the expression of immune stimulatory molecules and cytokines, as well as decreasing the expression of immunosuppressive molecules (such as IL-1A, IL-6, IL-8, IL-10) and reducing the number of regulatory immune cells (such as Tregs and MDSCs) [1]. They are mainly used for advanced cutaneous melanoma but also for other cancers such as non-small cell lung cancer.

Another strategy is to act on immune checkpoints that normally play a role in immune tolerance. Cytotoxic T lymphocyte antigen 4 (CTLA-4)–CD28 and programmed cell death 1 (PD-1)–programmed cell death 1 ligand 1 (PD-L1) are cell surface receptors that have an inhibitory effect on T cell response and therefore promote immune tolerance [1], [2]. Cancer cells take advantage of this mechanism to create a tolerant microenvironment for tumor cell proliferation. Therefore, immune checkpoint inhibitors target CTLA-4–CD28 and PD-1–PD-L1 axes to reestablish antitumor immunity [2]. They are used in advanced-stage melanoma and for solid organ tumors such as small cell lung cancer and non-small cell lung cancer, or renal cell carcinoma [2]. These revolutionary treatments lead to a higher response rate against cancer, especially with combined targeted therapy, but on the other hand, they can be associated with immune-related adverse events (irAEs). While these adverse events must be taken into consideration, other causes of ocular inflammation should also be ruled out.

Publication History

Received: 19 October 2022

Accepted: 21 December 2022

Article published online:
25 April 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
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