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

Abstract

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.