Inflammatory Microenvironment In Skin Cancer
Reference : PhD Mei LI
Publication de l'offre : 6 avril 2016
It has been recognized that immune cells in the tumor microenvironment not only fail to mount an
effective anti-tumour immune response, but also interact intimately with the transformed cells to aid in tumor growth and invasion. Manipulation of the patient’s immune system in the treatment of malignancies has been a goal of cancer for decades. Immunotherapies including cancer vaccines and immune checkpoint blockade which aim at restoring anti-tumor effects have proven to be novel therapies in treating metastatic tumors including melanoma, the deadliest skin cancer. However, the number of patients responding to current therapies is still limited. Indeed, investigation toward a better understanding the
inflammatory microenvironment associated with melanoma is crucially required for identifying new biomarkers predicting prognosis and clinical response to guide patient selection and therapeutic optimization, and providing novel targets to be added to cancer immunotherapy.
Emerging pieces of evidence have made signalling molecules involved in T heper type 2 (Th2) inflammation interesting but debating candidates in cancer therapy. A Th2 predominant has been shown in many types of cancers, which is suggested either to create a tumor-permissive or tumor-suppressive microenvironment. In the context of skin cancer, local and systemic Th2 polarization has remained elusive. Moreover, the
reciprocal interaction between cancer cells and their microenvironment in skin remains largely unknown.
Our previous research has built a strong background on cutaneous Th2 immunity in pathogenesis of cutaneous inflammatory diseases [1-3].
In this project, we will employ mouse models to characterize melanoma-associated inflammatory microenvironment, to elucidate the contribution of Th2 cellular and molecular components, in particular, the cytokine TSLP that we identified as a key player in Th2 inflammation, in tumor growth and
metastasis, and to further explore the therapeutic potential by reprograming the tumor-associated inflammation.
To achieve these goals, the project will employ mouse melanoma models, mouse genetic tools (e.g. gene knockout), tumor cell transplantation, signal blocking (e.g. by neutralizing
antibodies), specific cell depletion, cellular and immunological approaches (e.g. surface and intracellular staining, flow cytometry, cell sorting), molecular biological approaches (e.g. qRT-PCR, RNAseq) and histological analyses (e.g. immune-staining; confocal microscopy). We expect that insights obtained from this project will contribute to identify new biomarkers for melanoma prognosis, for predicting clinical response to
immunotherapy, and help to determine optimal therapeutic sequences and combinatorial strategies.
1. Li, J., et al., J . Allergy Clin. Immunol., 2016. in press.
2. Leyva-Castillo, J.M., et al., Nat Commun, 2013. 4: p. 2847.
3. Zhang, Z., et al., Proc Natl Acad Sci U S A, 2009. 106(5): p. 1536-41.
-COMPETENCES SOUHAITEES : We wish to integrate in the team a highly motivated, hard-working and collaborative PhD student. He/she should have solid knowledge in cellular and immunological biology, pathology, molecular biology, and have received training on mouse models, with great
enthusiasm on tumor pathogenesis. An excellent level of English speaking, reading and writing is required.
- EXPERTISES QUI SERONT ACQUISES AU COURS DE LA FORMATION : The student will acquire interdisciplinary research experience on inflammation and cancer, cytokine signaling, pathogenesis and functional mouse genetics. He/she will develop technique expertise flow cytometry, quantitative gene expression, deep sequecing, imaging as well as in vivo pathophysiology. He/she should also acquire scientific expertise on
designing, organizing and analyzing research experiments, oral presentation and paper writing.
Date limite de candidature : 31 décembre 2016