We attempt to propose a refined definition of the notion of tumor microenvironment and a better understanding of the metastatic process (including by revisiting the “seed and soil” hypothesis), especially considering the interactions between cancer and the immune system. A major feature of our approach is to explore cancer in its evolutionary context. When did cancer appear in evolution? Which extant organisms develop cancer? What types of cancer resistance have been developed in various organisms? We explore the connection between cancer and multicellularity, and ask to what extent cancer can be conceived as the result of a process of decohesion of the multicellular individual, an idea that combines cancer biology, immunology, developmental biology, evolutionary biology, and ecology. Cancer is an age-related disease, but it remains vague how age contributes beyond accumulation of mutations and various risk factors like inflammation and immunosenescence. Based on a general model of aging as the progressive loss of efficiency of mechanisms of maintenance in tissue homeostasis, we try to comparatively model the trajectories of the successfully aging tissue and of the cancerous tissue. These highly theoretical contributions are designed to harness research programs and maximize their chances of success.
Thomas Bosch, Bertrand Daignan-Fornier, Charlotte Domblides, Dorothée Duluc, Lucie Laplane, Nicolas Larmonier, Alberto Mantovani, Macha Nikolski, Samir Okasha, Anya Plutynski, Hamid Revzani, Vanja Sisirak, Pierre Soubeyran, Eric Vivier