The microenvironment, or niche, plays a key role in the initiation of cancer and growth of cancer cells, in the escape of these cells from physiological anti-tumor defenses and in their resistance to treatment.
Promoting research on the tumor microenvironment is essential to understand the pathophysiology of cancers and to develop new therapeutic strategies to limit the risk of metastases and relapse after treatment.
Paralleling the microenvironment and actors of the solid tumor and bone marrow niche.
On the left part of the diagram, the solid tumor is governed by cellular components such as healthy cells and tumor cells juxtaposed with immunosuppressive or neutral cancer-associated fibroblasts (CAFs) and myeloid-derived suppressor cells (MDSCs). The different gradients of oxygen, pH and growth factors (BMP2, BMP4) then participate in the tumor cell fate (proliferation, metastasis...). On the right panel, healthy hematopoietic stem cells (HSCs), bone marrow-mesenchymal stem/stromal cells (BM-MSCs) immune cells and tumor cells (attracted from a solid tumor by chemokine gradients such as CXCL12) or leukemia cells, quiescent or not, will be confronted with gradients of oxygen, pH, growth factors (BMP2, BMP4, SCF, APELIN) and cytokines (CXCL8, CXCL12, IL-1b) in a similar way as cells within the solid tumor. All these interrelations and interconnections, controls and feedbacks, will allow the tumor cell to proliferate and spread. Oxygen gradients, on the left, result from diffusion of oxygen from the blood vessels (vascular niche) as tumors grow outward from the local vascular architecture. On the right, there is a double gradient between arterioles and sinusoids. The cells will adapt their metabolism along these gradients and create, as a counterpart, a pH gradient due to the release of lactate and H+ protons. Bottom part: As crucial powerhouses for cell metabolism and tissue survival, mitochondria will transfer horizontally from stromal cells to cancer and/or immune cells, via nanotubes, EVs or freely, to allow recipient cells to adapt and modify their metabolism (mitochondrial respiration, ATP, pyrimidine synthesis) to meet different stresses (oxidative stress) and energy demands.
Ref: Frontiers in Immunology 2021, 12:766275
The story of FSTM
The will to federate French research forces on the cancer microenvironment has been progressively built up over the last 10 years through recurrent national think tanks in Tours (37), bringing together researchers, hematologists and oncologists.
The French National Center for Scientific Research (CNRS) has encouraged this process by labeling in 2015 the research group GDR 3697 MicroNiT "Microenvironment of tumor niches" gathering 19 INSERM and CNRS research units. This GDR has been renewed in 2019 with 26 research units.
The dynamic created has allowed to share experiences, to promote collaborations between teams and to set up ambitious research projects in order to reinforce the knowledge on the development of cancers and to propose new therapeutic leads targeting the tumor microenvironment.
This impulse will continue and be strengthened within the FSTM, which will promote interactions between researchers, physicians, patient associations, cancer organizations and pharmaceutical partners in order to improve cancer treatment.