Molecular Vulnerabilities of Tumor Escape in mature B-cell Malignancies

Team leaders : Catherine Pellat and David Chiron

Research projects

Hallmarks of cancer, which include dysregulation of cell cycle and apoptosis are both of tumor and of microenvironment origins. Although these hallmarks favor cancer survival and growth, they also confer specific addictions or vulnerabilities to cancer cells that can be exploited for therapies with regard to cancer heterogeneity and specificity.

We work on identifying vulnerabilities – Achille’s heel – that are consequent to the adaptation of cancer cells to survival and resistance within their ecosystem. More precisely, we focus on major molecular pathways involved in resistance/escape of cancer cells to death, such as p53 pathway and BCL2 network. We develop original culture models (ex vivo coculture models, PDX) and cutting-edge technologies (Multispectral IHC, multiparameter flow cytometry, scRNASeq). Our research models are mature B-cell malignancies such as Multiple Myeloma and Mantle Cell Lymphoma.
 

Contact

Catherine Pellat & David Chiron

Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes Angers

⌂ Institut de Recherche en Santé de l'Université de Nantes - 8 quai Moncousu - BP 70721 - 44007 Nantes cedex 1

✉ catherine.pellat-deceunynck@univ-nantes.fr
✉ david.chiron@univ-nantes.fr

✆ +332 28 08 02 98



 

Team certified the 04/08/21

Key publications

Decombis S, Papin A, Bellanger C, Sortais C, Dousset C, Le Bris Y, Riveron T, Blandin S, Hulin P, Tessoulin B, Rouel M, Le Gouill S, Moreau-Aubry A, Pellat-Deceunynck C, Chiron D. The IL32/BAFF axis supports prosurvival dialogs in the lymphoma ecosystem and is disrupted by NIK inhibition. Haematologica. (2022)

Le Gouill S, Morschhauser F, Chiron D, Bouabdallah K, Cartron G, Casasnovas O, Bodet-Milin C, Ragot S, Bossard C, Nadal N, Herbaux C, Tessoulin B, et al. Ibrutinib, obinutuzumab, and venetoclax in relapsed and untreated patients with mantle cell lymphoma: a phase 1/2 trial. Blood. (2021)

Seiller C, Maiga S, Touzeau C, Bellanger C, Kervoëlen C, Descamps G, Maillet L, Moreau P, Pellat-Deceunynck C, Gomez-Bougie P, Amiot M. Dual targeting of BCL2 and MCL1 rescues myeloma cells resistant to BCL2 and MCL1 inhibitors associated with the formation of BAX/BAK hetero-complexes. Cell Death Dis. (2020)

Papin A, Tessoulin B, Bellanger C, Moreau A, Le Bris Y, Maisonneuve H, Moreau P, Touzeau C, Amiot M, Pellat-Deceunynck C, Le Gouill S, Chiron D. CSF1R and BTK inhibitions as novel strategies to disrupt the dialog between mantle cell lymphoma and macrophages. Leukemia. (2019)

Lok A, Descamps G, Tessoulin B, Chiron D, Eveillard M, Godon C, Le Bris Y, Vabret A, Bellanger C, Maillet L, Barillé-Nion S, Gregoire M, Fonteneau JF, Le Gouill S, Moreau P, Tangy F, Amiot M, Moreau-Aubry A, Pellat-Deceunynck C. p53 regulates CD46 expression and measles virus infection in myeloma cells. Blood Adv. (2018)

Gomez-Bougie P, Maiga S, Tessoulin B, Bourcier J, Bonnet A, Rodriguez MS, Le Gouill S, Touzeau C, Moreau P, Pellat-Deceunynck C, Amiot M. BH3-mimetic toolkit guides the respective use of BCL2 and MCL1 BH3-mimetics in myeloma treatment. Blood. (2018)

Le Gouill S, Thieblemont C, Oberic L, et al., Rituximab after Autologous Stem-Cell Transplantation in Mantle-Cell Lymphoma. NEJM. (2017)

Leverson JD, Sampath D, Souers AJ, Rosenberg SH, Fairbrother WJ, Amiot M et al., Found in Translation: How Preclinical Research Is Guiding the Clinical Development of the BCL2-Selective Inhibitor Venetoclax. Cancer Discov. (2017)

Touzeau C, Le Gouill S, Mahé B, Boudreault JS, Gastinne T, Blin N, Caillon H, Dousset C, Amiot M, Moreau P. Deep and sustained response after venetoclax therapy in a patient with very advanced refractory myeloma with translocation t(11;14). Haematologica. (2017)

Chiron D, Bellanger C, Papin A, Tessoulin B, Dousset C, Maïga S, Moreau A, Esbelin J, Trichet V, Chen-Kiang S, Moreau P, Touzeau C, Le Gouill S, Amiot M, Pellat-Deceunynck C. Rational targeted therapies to overcome microenvironment-dependent expansion of mantle cell lymphoma. Blood. (2016)

Touzeau C, Ryan J, Guerriero J, Moreau P, Ni Chonghaile T, Le Gouill S, Richardson P, Anderson K, Amiot M, Letai A. BH3-profiling identifies heterogeneous dependency on Bcl-2 family members in Multiple Myeloma and predicts sensitivity to BH3 mimetics. Leukemia. (2015)

Chiron D, Di Liberto M, Martin P, Huang X, Sharman J, Blecua P, Mathew S, Vijay P, Eng K, Ali S, Johnson A, Chang B, Ely S, Elemento O, Mason CE, Leonard JP, Chen-Kiang S. Cell-cycle reprogramming for PI3K inhibition overrides a relapse-specific C481S BTK mutation revealed by longitudinal functional genomics in mantle cell lymphoma. Cancer Discov. (2014)

Tessoulin B, Descamps G, Moreau P, Maiga S, Lodé L, Godon C, Marionneau-Lambot S, Ouiller T, Le Gouill S, Amiot M, Pellat-Deceunynck C. PRIMA-1Met induces myeloma cell death independently of p53 by impairing the redox balance. Blood. (2014)

Touzeau C, Dousset C, Le Gouill S, Sampath D, Leverson JD, Souers AJ, Maïga S, Béné MC, Moreau P, Pellat-Deceunynck C, Amiot M. The Bcl-2 specific BH3 mimetic ABT-199 : a promising targeted therapy for t(11 ;14) multiple myeloma. Leukemia. (2014)

Job offers

Master 1

Master 2

PhD thesis

Post-doc