Project description
Shedding light on the melanoma immune mystery
Despite 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.
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 Our recent unpublished clinical and experimental findings uncover new, yet to be explored, melanosome contributions to cancer immunity unique to melanoma.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 latters 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 offer the scientific community new experimental tools and omics data on melanoma EVs and immunity. Finally, our project will provide new potential therapeutic means to overcome melanoma immunotherapy-resistance and block melanoma progression.
Fields of science (EuroSciVoc)
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CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
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Call for proposal
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(opens in new window) ERC-2022-ADG
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69978 Tel Aviv
Israel
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