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The Project
Concept
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Background

Cancer development involves complex interactions between cancer cells and their microenvironment, influenced by molecular pathways, immune cell interactions, and host factors like age, genetics, and environment. Immune signatures are potential prognostic indicators for solid tumors, impacting therapy success alongside local tumor microenvironment factors. Treatment approaches for solid tumors have shifted towards molecular-based strategies like immune checkpoint inhibitors (ICI), but response rates remain limited. Translational research is essential to understand tumor-host interactions, develop biomarker-driven treatments, and improve therapy strategies.

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The MULTIR Consortium aims to study tumor-host interactions across various tumor types and patient characteristics, collecting extensive clinical and molecular data to enhance understanding of treatment response mechanisms. Collaboration among specialists enables comprehensive analysis, with a focus on investigating immune-rich tumor types such as bladder, lung, and melanoma to identify potential targetable characteristics.

Melanoma:

In Western countries, melanoma has seen the most significant rise in cancer incidence over the past five decades, doubling every decade. This cancer claims the lives of over 20,000 individuals annually in Europe alone. Accurately predicting the response to immunotherapy is imperative in melanoma treatment to determine the most suitable initial systemic approach for each patient. However, there remains minimal guidance for selecting the optimal therapy for each individual patient.

Lung Cancer:

 Lung cancer encompasses a diverse range of diseases, including small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), the latter constituting 80-85% of cases. Therapeutic resistance, whether inherent or acquired, is likely fueled by tumor evolution, which is facilitated by the extensive genetic and epigenetic variations observed in NSCLC. A comprehensive molecular examination of NSCLC combined with thorough histological characterization offers a pathway to deepen our understanding of the disease's clinical presentations, including responses to therapy. This, in turn, enables the more effective utilization of current treatments or combinations thereof, as well as the exploration and development of novel therapeutic strategies.

Bladder Cancer:

Muscle Invasive Bladder Cancer (MIBC) marks the advanced phase of bladder cancer. Currently, there hasn't been a systematic examination of the interplay among the tumor, tumor immune microenvironment (TIME), and broader host-related factors, and how these interactions influence clinical development and response outcomes. Moreover, despite advancements in cancer treatment, survival rates for MIBC have remained stagnant for the past three decades. Additionally, the ability to predict response to immunotherapy in MIBC patients remains elusive.

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MULTIR’s  efforts include investigating social, ethnic, and cultural aspects beyond molecular features and utilizing advanced technologies for omics data generation. Data compilation is facilitated by experts in databasing, adhering to EU policies for data sharing and open access. Furthermore, bioinformatics, mechanistic modeling, and AI experts are involved in identifying relevant features and molecular processes associated with treatment response.

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The knowledge generated will be verified in relevant model systems, with a focus on reducing animal experimentation. Industrial partners and experts in consortium management contribute to efficient implementation of results, while patient organizations ensure alignment with patient perspectives for personalized treatments.

Implementation

In order to achieve the successful complementation of MULTIR objectives,

the work-plan is wisely organized and split into the following distinct Work Packages (WPs):

  • Work package WP2 – Data space: platform development and management
    Objectives The goal of WP2 is to develop the MULTIR data space for data sharing and curation, and ensure data privacy, and protection. The objectives are: (i) application of advanced cybersecurity, data privacy and protection measures, (ii) developing a European healthcare data space, its soft-infrastructure, and de-centralised governance mechanism, (iii) development of digital tools for data analyses and modelling, and (iv) integration of the digital tools and data space and their deployment to the use cases.
  • Work package WP1 – Project management
    Objectives The goal of WP1 is to ensure effective communication among partners and information exchange within MULTIR Consortium. The objectives are: (i) establishing a management structure; (ii) organisation of project meetings; (iii) submission of reports and financial statements; (iv) management of ethical and legal obligations; and (v) organisation of sample and data exchange and (vi) set up of a Data Management Plan (DMP).
  • Work package WP3 – Clinical, pathology, molecular, immunology and imaging data: integration of existing and newly acquired datasets
    Objectives The goal within WP3 is to gather, align and curate existing datasets, available through: a) MULTIR participants’ access to large studies and datasets with long follow-up and through, b) systematic literature search, and subsequently integrate and analyse them according to MULTIR clinical endpoints. Generation of new molecular and single cell datasets is also foreseen including from newly developed omics platforms.
  • Work package WP7 – Dissemination, outreach and exploitation
    Objectives The main objectives of WP7 are to: (i) raise awareness of the project and its role in health promotion and improved management of melanoma, lung cancer and bladder cancer patients; (ii) disseminate novel findings; (iii) Increase the scientific and societal impact through effective dissemination and communication of project knowledge, standards and results during and after the project duration; (iv) Support potential exploitation of the project results and (v) assure proper handling of IPR. As part of the “Understanding (tumour-host interactions)”cluster, the project will contribute to the annual cluster meeting addressing common scientific challenges, organised in close collaboration with the European Commission.
  • Work package WP4 – Modelling tumour host interactions and response
    Objectives The primary objective of WP4 is to obtain a comprehensive understanding of immunological factors associated with tumour host interactions during oncological treatment. We will initially investigate single data layers and cellular components to identify key tumour host interactions. Furthermore, we will expand this work and construct and validate prediction models utilizing a variety of techniques. The goal for these models is to understand the interplay of risk factors with the molecular and immunological background and ultimately support prevention, screening and early detection demonstrating benefit for patients by improving survival.
  • Work package WP6 – Stakeholder engagement
    Objectives Within WP6 the goal is to ensure the acceptability and adoption of risk prediction information and risk calculators, including the tools developed by MULTIR, by a broad range of stakeholders including patients, lay people, health care professionals and policymakers.
  • Work package WP5 – Validation of the computational models and testing of optimised treatments
    Objectives Within WP5 the goal is to validate the MULTIR models and delineated tumor host interactions.
  • Work package WP8 – Ethics requirements
    Objectives The objective is to ensure compliance with the 'ethics requirements' set out in this work package.
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