Project: C04

Tumor-microenvironmental alterations during pathogenesis and therapy of conjunctival melanoma

Conjunctival melanoma (CM) is a rare and potentially fatal malignant tumor on the mucosa of the ocular surface. The molecular and cellular nature of CM, however, is still largely unknown. Due to some similarities to the better-studied cutaneous melanoma, novel therapies for cutaneous melanoma, such as immune checkpoint inhibitors, may benefit patients with metastatic CM. Checkpoint inhibitors promote inflammation and thus the antitumor immune response. To date, only case reports of metastatic CM patients treated with immunotherapy have been published. Hence, there is an urgent need to better understand the immunological responses against CM and to define new therapeutic targets. Our research hypothesis addresses immunomodulatory therapies in CM and understanding the immunological background of the disease, particularly the cellular and molecular aspects of the tumor microenvironment (TME). The TME has a critical impact on carcinogenesis by promoting protumoral immunosuppression and contributing to metastasis and tumor angiogenesis. Published and preliminary work by our groups shows that inflammatory cytokines, particularly osteopontin (OPN) and interleukin-6 (IL-6) as well as dendritic cells (DCs) are important in carcinogenesis of various tumors We therefore hypothesize that inflammatory cytokines such as IL-6 and OPN are essential for CM and represent a therapeutic target. To confirm the hypothesis, the student will employ techniques including transgenic models, single nucleus sequencing, transgenic mouse models, melanoma mouse models, transcriptional profiling, immunocytochemistry, in vitro functional assays, FACS analysis.