The Institut de Recherche en Cancérologie de Montpellier (IRCM) in Partnership with a biopharmaceutical company offers one PhD position.
Title : Targeted radionuclide therapy against cancer-associated fibroblasts: role of intercellular communications between CAFs, tumor and immune cells
Host laboratory : INSERM U1194 Montpellier (France)
Starting date : 01/10/2020
Key words : Cancer associated fibroblasts, secretome analysis, immune response, targeted radionuclide therapy, PDAC
Context :
It is now admitted that cancer therapy cannot be only restricted to cancer cells but must also consider the tumor cells microenvironment (TME) as it can promote resistance of cancer cells to such therapies. Therefore, novel treatment strategies should combine anticancer and anti-stroma agents. The TME or stroma is a complex ecosystem consisting of an extracellular matrix scaffold populated by endothelial cells, immune cells, as well as activated fibroblasts, termed cancerassociated fibroblasts (CAFs). TME components enter into a dynamic crosstalk involved in multiple stages of cancer development including tumor initiation, progression, and metastasis. Fibroblasts are spindle-shaped, non-epithelial (cytokeratin−, E-cadherin−), non-endothelial (CD31−) and non-immune (CD45−) cells of a mesenchymal lineage origin (vimentin+) in normal tissue where they are considered as quiescent cells with negligible metabolic and transcriptional activities. Conversely, resident fibroblast may become activated during processes such as wound healing, acute or chronic inflammation or tissue fibrosis but also in the context of cancer, considered as a “wound that never heals”. Their activation is then dependent on growth factors released by the cancer cells and also by infiltrating immune cells. CAFs represent one of the most abundant stromal cell types of several carcinomas including pancreatic cancers where 60–70% of the tumor tissue is composed of a desmoplastic stroma characterized by extensive collagen deposition and activated CAFs. Morphology and spatial distribution are key determinants in order to identify fibroblasts in a resting or activated state. Different markers, which are lower or not expressed by their normal counterparts, can also be used to identify activated fibroblasts such as α-smooth muscle actin (α-SMA), fibroblast- specific protein-1 (FSP-1), fibroblast-activation protein (FAP), PDGF receptors PDGFR) α or β, neuron-glial antigen-2 (NG2), periostin (POSTN), podoplanin (PDPN), tenascin-C (TNC).
Objectives :
The aim of this PhD project is to investigate, in preclinical PDAC tumors models, the biological response of CAFs to targeted radionuclide therapy and to investigate the intercellular communications between CAFs, tumor and immune cells.
Selection criteria :
We are looking for a motivated candidate with a strong biology background. Experience with cancer associated fibroblast culture and extraction would be highly appreciated. Animal handling experience would be also an advantage. Background in radiation biology is not a prerequisite. International student are welcome to apply.
If you are interested in this PhD position at the IRCM, please send your application :
- most recent CV
- motivation letter stating your previous research experience
- name/phone/email of at least one reference
To : jean-pierre.pouget@inserm.fr and sophie.poty@inserm.fr
Deadline : 31/07/2020
