Cancer Immunotherapy and Uveitis: Balancing Anti-Tumor Immunity and Ocular Autoimmunity

Abstract

While immune checkpoint inhibitors can lead to anti-tumor effect, they can also have numerous side effects (irAEs) that range in severity and can affect numerous organ systems. While the exact mechanism has not been elucidated, it is thought to be due to the disruption of the Cancer Immunotherapy and Uveitis ' 51

Germline genetic variants are associated with development of insulin-dependent diabetes in cancer patients treated with immune checkpoint inhibitors

“…14 One report demonstrated T-cell clones from a VKH patient targeting melanoma cells, suggesting similarity between epitopes. 15 Here, we studied RNA expression and mutations, and whole exome tumor and germline sequencing of tumor samples, to determine the possible contribution of tumor overexpression, tumor neoantigens, or germline genetic mutations to the development of ICI-DM.…”

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

“…The irAEs are broad and can affect a multitude of organs such as pneumonitis, encephalitis, myocarditis, hepatitis, colitis, and many others [2]. The ocular irAEs remain rare and have been reported in 1 % of patients [1,4]. The most encountered ocular irEAs are uveitis and sicca syndrome [2].…”

“…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].…”

“…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].…”

“…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.…”