Multiscaling approaches to identify predictors of cancer patient outcomes
This program aims to understand how interactions between tumor cells and their environment influence tumorigenesis and response to treatment, through multidimensional analyses. The interaction between tumor cells and their microenvironment will be studied in 1D and 2D, then in 3D using ex-vivo modeling and animal models. Repeatability of experimentation over time will enable us to reach 4D, while 5D will enable us to study the impact of environmental factors on tumor biology. These data will be integrated and interpreted thanks to 2 new platforms that will be developed to foster dialogue between physicians and researchers.
It is now well established that the invasiveness of a tumor is defined not only by its genetic alterations, but also by its interactions with its environment. The SIRIC CARPEM research teams have made a major contribution to showing that cancer is now considered as a real ecosystem of cells (cancerous, immune and stromal) interacting with the whole body of the tumor host. Deciphering these interactions is essential to defining new therapeutic strategies for curing cancer.
The research teams associated with CARPEM have major expertise in genomics, immunology, metabolism and physiology, and in the development of spatial imaging1. The combination of these areas of expertise will promote a multidimensional approach to understanding the various interactions of tumors with their environment, and enable the identification of new biomarkers.
1Gougelet et al. Gastroenterology 2019, Senni et al. Gut 2019, Yang et al. Nature Med 2019, Bondu et al. Sci Transl Med 2019, Roumenina et al., Cancer Immunol Res 2019, Petitprez et al. Nature 2020, Trentesaux et al. PNAS 2020 Legoff et al, Blood 2021, Paillet et al. J Exp Med 2021, Cadoux et al. J Hepatol 2021, Kantari-Mimoun et al. Cancer Immunol Res 2021, Passaro et al. Cell Rep 2021, Donne et al. Dev cell 2022, Bayard et al. Cancer Res 2022, Decroocq et al. Leukemia 2022, Molina et al. J Hepatol 2022, Trepo et al. Lancet Oncol 2022, Meylan et al. Immunity 2022, Italiano et al. Nature Medicine 2022
This research program is divided into 3 workpackages.
WP1 “Interaction and plasticity between cancer molecular subtypes and the immune microenvironment in 1 and 2D”. This workpackage aims to understand the mechanisms of interaction between tumor molecular subtypes and their microenvironment to better predict disease progression and response to treatment.
WP2 “2D to 4D models that recapitulate cancer ecosystems of interest – Innovative models”. This workpackage will focus on the development and use of 2D and 3D experimental models that recapitulate the cancer ecosystem. These models will provide a better understanding of the reciprocal dialogue between tumor cells and microenvironment cells, and consequently of the mechanisms of tumor initiation, progression and resistance to treatment.
WP3: “Impact of environmental factors on tumor biology, a fifth “ecological” dimension”. The aim of this workpackage is to understand the impact of environmental factors on tumor biology, in a genetically defined context, including the study of the host and its exposure to viruses or carcinogens. This will enable us to better assess the risk of developing cancer, and to adapt the surveillance of at-risk individuals.