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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - META-CAN (Targeting the metabolism-immune system connections in Cancer)

Teaser

Summary

Regardless of the tissue of origin, 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 provides 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 complementary set of hypothesis-driven research projects that focus 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. Crucially, clinical trials using metabolic inhibitors gave mixed results in cancer patients, because we do not know yet the rules of this interaction. In this sense, META-CAN will improve the understanding of these metabolic pathways in cancer in their dialogue with immune cells. 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 has 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 cross-talk 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.

Work performed

The primary objective of the META-CAN network is to provide the ESR students with a multidisciplinary scientific training in the frame of excellent scientific projects with non-academic networking possibilities. After their PhD degree, our trainees will be ready to embark on careers in academic, clinical, business or social organizational environments. In addition to traditional scientific skills (laboratory and writing expertise), META-CAN incorporates diverse aspects that will qualify the students for the impending future of international science-based society. Skills such as Communication, Creativity and Entrepreneurship are enhanced through participation in our network events, of which we have already celebrated two in which the ESRs have presented their results to an expert audience. Entrepreneurship and business training will be enhanced in future activities through dedicated complementary training by a top-rated Business School (ESADE), but also thanks to contact with our institutionâ€™s Technology Transfer Offices as part of a dedicated Work Package managed by an IPR committee.

In terms of research progress, all ESRs have already started their projects, delivering many results which are just submitted or now being prepared for publication in Open Access journals. Due to sensitive results we will not be able to make them public until they are published in peer-reviewed journals. Importantly, the research of one of our ESRs has already been published in JAMIA Open (entitled: Inferring new relations between medical entities using literature curated term co-occurrences). In addition, our IPR committee has evaluated patentability of results and one of our sub-projects might be of interest in that sense. We have also participated in multiple outreach activities, including some activities together with other ITNs, to improve visibility of European funded research among the general public. 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 has been in Leuven this last September 2019 (Mouse and organomimetic models of cancer and bioinformatics approaches in research) with around 50 attendees and many relevant talks on the topic.

Translational research is an integral part of our network and our ESRs are already embedded in a translational and entrepreneurial mindset thanks to the complementarity of our non-academic beneficiary partners. Apart from technical training in advanced state-of-the-art methodology relevant to the projects, METACAN provides ESRs with an invaluable personal network of contacts and collaborators, including non-academic specialists from the commercial, non-profit, clinical and publishing disciplines, which will benefit their employability. The ESRs have already undergone training in communication skills to several audiences, gender policies and ethics in research, research partnership, metabolomics, Seahorse methodology and biostatistics.

Final results

A common features of cancer cells is their ability to reprogram their metabolism and to escape immune regulation. META-CAN aims to address current limitations in cancer treatment through an innovative research program. META-CAN will lead with the identification and development of novel biomarkers and drugs for improving diagnostic and therapeutic approaches for cancer treatment. META-CAN brings together academic researchers, clinicians and the private sector establishing a network of excellence that integrates expertise in cancer models, study of metabolism and immune cell functions and drug and diagnostics development. This network will promote, facilitate and accelerate the translation of basic metabolic/immune response research to clinical and commercial outputs. To achieve this, META-CAN will go 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 provides complementary expertise to the program, is meaningful for achieving the research aims and provides private sector experience to all ESRs.

META-CAN will provide young researchers with ample multidisciplinary training in the various fields associated with cancer microenvironment and metabolism as well as it will provide them with skills necessary for the practical implementation of their research findings. Our research topic is innovative as it combines many of the Hot Topics in cancer research (Cancer Metabolism, Immunometabolism, Cancer Immunity) that are framing the future of cancer treatment.