📋 Tender Overview
Melanosomes As Cancer Immune Modulators: A Novel Paradigm In Melanoma Immunity
Shedding Light On The Melanoma Immune Mysterydespite Remarkable Strides In Treating Melanoma, Half Of The Patients Face Treatment Resistance And Recurrence. Recent Discoveries Reveal Untapped Potential In Contributions From Melanosome To Cancer Immunity Unique To Melanoma. Melanosomes, Large Extracellular Vesicles Containing Melanin, Surprisingly Inhibit T-Cell Activity And Carry Distinct Neoantigen Signatures. In This Context, The Erc-Funded Melanosomeevimmune Project Will Explore Melanosome Interactions With T-Cells, Their Influence On Immune Recognition, And Their Interaction With Macrophages. Through Advanced Research Tools And Models, The Project Will Shed Light On Melanoma Progression And Therapy Response. The Findings Will Advance Our Understanding Of Extracellular Vesicles In Various Physiological Systems. Overall, The Project Holds Promise For Novel Therapeutic Approaches Against Melanoma Resistance And Progression.
Funded Under
European Research Council (Erc)
Total Cost
€ 2 515 625,00
Eu Contribution
€ 2 515 625,00
Coordinated By
Tel Aviv University
Israel
Start Date
1 January 2024
End Date
31 December 2028
Objective
Despite remarkable progress in treating melanoma, the most lethal of human skin cancers, 50% of patients are treatment-resistant, with most experiencing disease recurrence. Our recent unpublished clinical and experimental findings uncover new, yet to be explored, melanosome contributions to cancer immunity unique to melanoma. Melanoma retains, for mostly unknown reasons, the ability of its origin to produce melanosomes, lineage-specific large extracellular vesicles (EVs) containing melanin. Surprisingly, our preliminary findings indicate that melanosomes bind and block T-cell activity in a T-cell receptor/antigen-dependent manner; melanosomes carry a neoantigen signature that is distinct from their cell of origin; and can be recycled by stoma cells, with each type endowing the melanosomes with a distinct signature, which may modulate, upon engulfment by macrophages, the latter’s phenotype in relation to melanoma.
Given our novel findings and body of literature that strongly suggest an immune role for melanosomes, we here propose to comprehensively explore, for the first time, melanosomes’ effect on melanoma immunity in three directions: melanosomes’ interaction with T-cells (Aim 1), influence on melanoma immune recognition (Aim 2) and interaction with macrophages (Aim 3). This will be achieved by a strong research framework involving new experimental tools, fresh human samples, and cutting-edge in-vivo, molecular, cellular and computational models.
While of tremendous complexity and scale, this project is set to offer new perspectives on melanoma progression and response to therapy. Further, our novel EV concepts will greatly advance the EV field and can also be applied to other physiological systems. Our project will also off
