2-year post-doctoral position in Cordeliers Research Center
Team and location:
Team “Cancer, Immune Control and Escape”, Cordeliers Research Center(INSERM UMRS1138), Paris, FRANCE.
Supervisor : Pr. Isabelle CREMER (PhD, PU University Pierre et Marie Curie).
Context and environment:
The team “Cancer, Immune Control and Escape”, of Cordeliers Research Center is an academic research structure affiliated with INSERM (French Institute of Biomedical Research), University Pierre et Marie Curie, and University Paris Descartes, located in the center of Paris.
The team is interested in deciphering the immune microenvironment of solid tumors and its interactions with tumor cells to find new prognosis markers and predictive markers of the therapeutic response, and to identify tumor drivers of the immune contexture.
Epidemiological studies have examined a potential link between respiratory infections, chronic inflammation and lung cancers. In line with these studies, chronic bronchitis, pneumonia and emphysema are all consistently associated with an increased risk of lung cancer. Toll-Like Receptors (TLR) have been linked to inflammation in several tumor models. Some of these TLR recognize viral nucleic acid, such as TLR7, which is a receptor for viral single-stranded RNA. Viral recognition by TLR7 induces activation of IRF, NF-kB and MAPK signaling pathways, leading to secretion of type I interferon and inflammatory cytokines. The team has previously demonstrated that TLR7 is expressed by tumor cells of NSCLC patients, and that high TLR7 expression confers poor clinical outcome and poor response to chemotherapy. In vitro TLR7 stimulation of lung tumor cell lines by synthetic agonists induced NF-kB activation, increased expression of Bcl-2, had a pro-tumoral effect, and conferred resistance to platinium-based chemotherapy. These pro-tumoral effects were confirmed in lung tumor mice models.
Based on these premises, we hypothesize that virus infection of lung tumors can lead to activation of TLR7-mediated signaling pathway, hence promotes pro-tumoral effect and resistance to anti-tumoral treatments. The candidate will study the effects of respiratory virus infection on tumor progression (growth, metastasis and response to treatment), as well as on tumor immune microenvironment (composition, activation and function of immune cells). Thiswill be explored using tumor mice models and lung tumor cohorts of patients. This project will benefit from access to blood, and lung tumors samples from patients. The candidate will benefit from CRC core facilities.
Cherfils-Vicini J, Platonova S, Gillard M, Laurans L, Validire P, Caliandro R, Magdeleinat P, Mami-Chouaib F, Dieu-Nosjean MC, Fridman WH, Damotte D, Sautès-Fridman C, Cremer I. (2010)Triggering of TLR7 and TLR8 expressed by human lung cancer cells induces cell survival and chemoresistance. J Clin Invest. 120:1285-97.
Gillard-Bocquet M, Caer C, Cagnard N, Crozet L, Perez M, Fridman WH, Sautès-Fridman C, Cremer I. (2013) Lung tumor microenvironment induces specific gene expression signature intratumoral NK cells. Front Immunol. 4:19.
Platonova S, Cherfils-Vicini J, Damotte D, Crozet L, Vieillard V, Validire P, André P, Dieu-Nosjean MC, Alifano M, Régnard JF, Fridman WH, Sautès-Fridman C, Cremer I. (2011) Profound coordinated alterations of intratumoral NK cell phenotype and function in lung carcinoma. Cancer Res. 71:5412-22.
Chatterjee S, Crozet L, Damotte D, Iribarren K, Schramm C, Alifano M, Lupo A, Cherfils-Vicini J, Goc J, Katsahian S, Younes M, Dieu-Nosjean MC, Fridman WH, Sautès-Fridman C, Cremer I. (2014) TLR7 promotes tumor progression, chemotherapy resistance, and poor clinical outcomes in non-small cell lung cancer. Cancer Res. 74:5008-18.
Fucikova J, Becht E, Goc J, Iribarren C, Remark R, Damotte D, Alifano M, Fridman WH, Dieu- Nosjean MC, Kroemer G, Sautès Fridman C, Cremer I. (2016) Calreticulin is a powerful prognostic marker for survival of non-small-cell lung cancer patients. Cancer Res. 76:1746-56.
Appointment is for 2 years and funded by Institut National du Cancer.
Candidate profile:We are looking for motivated PhD or an MD-PhD with experience in tumor immunology and possibly in virology. Candidates must have a strong interest in oncoimmunology with a previous experience in this field. Skills in flow cytometry, cell culture, histology and animal models are required.
• Ph.D. in immunology
• Strong background in tumor immunology
• Experience with mice models
• Track record of innovative research and scientific publications
• Autonomy in the organization of the work
• Basic knowledge in biostatistics and bioinformatics tools
Applications must include a CV with a cover letter and contacts for 2 references. Please send
your applications to: email@example.com