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Targeting the metabolism-immune system connections in Cancer

Periodic Reporting for period 2 - META-CAN (Targeting the metabolism-immune system connections in Cancer)

Okres sprawozdawczy: 2019-09-01 do 2021-08-31

While extremely diverse in origin, all cancer cells show common features of profound metabolic changes and escape from the immune system. It is now obvious that metabolic adaptations are not limited to glucose metabolism (Warburg effect) but are more general and affect several metabolic pathways in cancer cells but also in surrounding, non-malignant immune cells. Understanding how metabolism can affect tumor cells and the anti-cancer immune response therefore represents a potential therapeutic intervention point that can be exploited for a wide range of tumors. However, the development of such therapies is hampered by the complexity of cellular metabolism and the immune system, plus a shortage of scientists with interdisciplinary training that can navigate with ease between academic, industrial, and clinical sectors. Our network has provided a pan-European interdisciplinary and intersectoral training programme of excellence, bringing young researchers together with world-leading academics, clinicians, and industry personnel. The consortium integrates a coherent set of hypothesis-driven research projects that are aimed at focusing on ONE question: how metabolism is associated with modulation of cell death susceptibility and the immune response in the context of cancer.

Much effort has been devoted to understanding how modulating cell metabolism may interfere with tumor growth. While the basic pathways have been worked out, we now need to better understand them in terms of their interactions between cancer and immune cells. This lack of knowledge hinders efforts to exploit inhibition of cancer metabolism for therapeutic and diagnostic purposes. META-CAN has improved (and surely will in the future) the understanding of these metabolic pathways in cancers in their dialogue with immune cells and has made great advances in the pre-clinical validation of new targets and metabolic drugs. This will serve as a platform for drug discovery and diagnostics efforts that aim to therapeutically target metabolism, inflammation, or immune responses for the treatment of a variety of cancers.

Specifically, this program had the following research objectives:
1.- Uncover the effect of inhibition of metabolism on tumor cells.
2.- Delineate the effects of nutrient-poor and hypoxic microenvironment on the crosstalk of tumor-associated innate immune cells.
3.- Reveal the impact of nutrient microenvironment on tumor cells and lymphocytes.
4.- Develop anti-metabolic drug and diagnostic markers.
Our network has provided 15 early-stage researchers (ESRs) with high quality scientific training involving the integration of multiple newly emerging and state-of-the-art disciplines. After their PhD degree, our trainees will be ready to embark on careers in academic, clinical, business, or social organizational environments. In addition to technical training in advanced state-of-the-art methodology relevant to the projects (Seahorse methodology by Agilent, metabolomics by Technion, and biostatistics by VIB), META-CAN has incorporated diverse aspects that qualify the students for the impending future of international science-based society. Skills such as Communication and Creativity have been enhanced through participation in our network events and the dedicated trainings offered by our partner organizations (Cancéropôle and BIOcomuniCA’T). The ESRs have also been exposed to other important aspects such as gender policies, ethics in research, and research partnership. Entrepreneurship and business training have been enhanced through a dedicated complementary training by a top-rated Business School (ESADE), but also thanks to contact with our institution’s Technology Transfer Offices and the rest of non-academic beneficiaries of the project. METACAN has also provided ESRs with an invaluable personal network of contacts and collaborators, including non-academic specialists from the commercial, non-profit, clinical, and publishing disciplines (Nature Publishing Group and The FEBS Journal), which will benefit their employability.

In terms of research progress, all project deliverables have been submitted and despite the experienced risks (mainly the outbreak of COVID-19), thanks to the mitigation measures implemented, all ESRs have been able to satisfactory accomplish most objectives proposed in their research plan. Many of the results obtained have already been published in top-rated journals (such as PNAS, Nature Cancer or Cell Metabolism). The rest of the results are now being prepared for publication in Open Access journals. Due to sensitive results (some results are being evaluated by the respective institutional IPR experts as well as the consortium IPR committee), we will not be able to make them public until they are published in peer-reviewed journals and/or patents are filled.

We have also participated in multiple outreach activities, including some activities together with other ITNs, to improve visibility of European funded research among the public. Some of our ESRs have also been involved in educational activities, such as organization of courses and giving seminars to high school students. We have organized two international meetings with high attendance that have benefitted the European Research area. The first one was in Nice during April 2018 (C3M META-CAN Inflammation & Disease Symposium) with several keynote speakers and over 200 attendees. The second one was in Leuven in September 2019 (Mouse and organomimetic models of cancer and bioinformatics approaches in research) with around 50 attendees and many relevant talks on the topic. We have also organized an international EMBO Workshop (Cancer Immunometabolism) as our final event which will take place in November 2021 in Sitges, Barcelona.
A common features of cancer cells is their ability to reprogram their metabolism and to escape immune regulation. META-CAN has addressed current limitations in cancer treatment through an innovative research program. META-CAN has made advances by identifying new biomarkers and studying the use of novel drugs that will improve diagnostic and therapeutic approaches for cancer treatment in the future. As an important remark, research performed at VIB within the META-CAN project has been featured in the EU H2020 - Innovation Radar website and selected for presentation at the “Cluster Event on Cancer Research and Innovation” organized by MSCA. Other projects are pending few validations to move forward from pre-clinical stages but will surely improve Cancer therapeutics.

This network has promoted, facilitated, and accelerated the translation of basic metabolic/immune response research to clinical and commercial outputs. To achieve this, META-CAN has gone significantly beyond state-of-the-art by integrating methodologies from the fields of molecular and cellular biology, disease models, drug discovery and diagnostics, early clinical studies, and network analysis. The level of involvement of industry and clinical partners in the META-CAN network has provided complementary expertise to the program.

Finally, META-CAN has provided young researchers with ample multidisciplinary training in the various fields associated with cancer microenvironment and metabolism. Our ESRs have acquired a professional profile that will allow them to improve future research and discovery in the fields of cancer, metabolism, and immune system.
Second META-CAN Workshop in Leuven
First Management Meeting in Nice
First Management Meeting in Nice