CORDIS
EU research results

CORDIS

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Imaging, characterizing and targeting metastatic niches in melanoma

Project information

Grant agreement ID: 884699

Status

Grant agreement signed

  • Start date

    1 December 2020

  • End date

    30 November 2025

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 2 497 945

  • EU contribution

    € 2 497 945

Hosted by:

FUNDACION CENTRO NACIONAL DE INVESTIGACIONES ONCOLOGICAS CARLOS III

Spain

Objective

Melanomas are the only tumors where lesions barely over one millimeter in depth can be at risk for metastasis. An increasing number of (epi)genetic alterations and mechanisms of immune evasion have been identified in this disease. Nevertheless, no molecular biomarker has been approved as a bona fide prognostic indicator. Progress in this field has been hampered by the paucity of models to visualize premetastatic niches in vivo, and monitor relapse after surgery. We have overcome these limitations by generating reporter mouse strains to “illuminate” premetastatic niches. Specifically, our “MetAlert” mice were designed for whole-body imaging of the aberrant expansion of the lymphatic vasculature, an early event that precedes metastasis. MetAlert, together with functional studies in human cells and histopathological validation in clinical biopsies, revealed the growth factor MIDKINE as a new melanoma-secreted prometastatic driver. We have now discovered roles of MDK as an immune suppressor, and identified a MDK-associated transcriptional profile that separates patients with a distinct expression of alarmins and bacterial response factors. Proteomic analyses revealed a set of additional factors secreted by aggressive melanoma cells, but their specific contribution to premetastatic niches is unclear.

Here we will exploit our MetAlert and novel imaging reporters we have generated for a comprehensive spatio-temporal and functional analysis of premetastatic niches in vivo (including and beyond MDK). We will define how melanomas act “at a distance” before metastasis (Aim 1), and evade the immune system at different anatomical sites (Aim 2). Aim 3 will dissect the impact of the microenvironment, particularly via alarmins. Aim 4 will pursue the therapeutic targeting of metastatic niches (pre and post-surgery) with immunomodulators we discovered (and have led to clinical trials), and by targeting vulnerabilities that we found distinguish melanoma from other diseases.
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Host institution

FUNDACION CENTRO NACIONAL DE INVESTIGACIONES ONCOLOGICAS CARLOS III

Address

Calle Melchor Fernandez Almagro 3
28029 Madrid

Spain

Activity type

Research Organisations

EU Contribution

€ 2 497 945

Beneficiaries (1)

FUNDACION CENTRO NACIONAL DE INVESTIGACIONES ONCOLOGICAS CARLOS III

Spain

EU Contribution

€ 2 497 945

Project information

Grant agreement ID: 884699

Status

Grant agreement signed

  • Start date

    1 December 2020

  • End date

    30 November 2025

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 2 497 945

  • EU contribution

    € 2 497 945

Hosted by:

FUNDACION CENTRO NACIONAL DE INVESTIGACIONES ONCOLOGICAS CARLOS III

Spain