Equipe 14 : Plasticity of tumoral Ecosystem after Radiobiology and Immunotherapy

The classical therapeutic scheme for neural cancers, such as Glioblastoma and Neuroblastoma, involved surgery followed with a combination of radio- and chemotherapies. However tumor location and acquired treatment resistance limit the efficacy of these treatments. Novel non-genotoxic therapeutic approaches in combination with actual treatments are currently being explored to improve their efficacy.

On this basis, the PETRI team explores 2 key parameters involved in tumor aggressiveness and relapse, tumoral metabolic adaptation and tumoral microenvironment cooption.
Our research program is organized around four main axis :
1)Impact of microvascular dysfunctions in tumor response to radiotherapy and relapse
2) Reciprocal impact of metabolic adaptation, microenvironment, and radiotherapy in the tumor ecosystem
3) Development of innovative immunotherapeutic strategies through antibody and T-cell engineering
4) Improvement of radiotherapy efficacy through innovative immunotherapeutic approaches

Personnes

F. Paris, DR INSERM

C. Pecqueur, DR CNRS, HDR
S. Birklé, PU, HDR
C. Gratas, MCU-PH, HDR
S. Fougeray, MCU
D. Leonetti, Ingénieure ICO
S. Goude, INSERM Staff Engineer
L. Durand,INSERM Staff Engineer
N. Galopin, CDD Engineer
M. Bahri, PhD student
H. Estephan, PhD student
O. Renoult, PhD student
P. Thomas, PhD student
G. Alzial, Master 2 student
J. Vignau, Master 2 student
G. Campard, Master 2 student

Chercheurs Associés
E. Rio, PH-ICO
A. Lisbona, PH-ICO
E. Thebaud, PH-CHU

Chefs de projets

Dr. François Paris, Ph.D., HDR, DR2 Inserm
Projet : Paracrine response of endothelial cells after radiotherapy

Dr. Claire Pecqueur, PhD,HDR, DR2 CNRS
Projet : Metabolic targeting in tumors

Dr. Stéphane Birklé, D.V.M./Ph.D., HDR, Professeur des universités, Faculté de Pharmacie
Projet : anti-OGD2Ac immunotherapy in Neuroblastoma

Dr. Sophie Fougeray, Pharm.D./Ph.D., Maître de conférences des universités, Faculté de Pharmacie
Projet : Optimization of anti-OGD2Ac immunotherapy with radiotherapy in Glioblastoma

Principales publications

Chauvin C, Joalland N, Perroteau J, Jarry U, Lafrance L, Willem C, Retière C, Oliver L, Gratas C, Gautreau-Rolland L, Saulquin X, Vallette FM, Vié H, Scotet E and Pecqueur C. NKG2D controls natural reactivity of Vγ9Vδ2 T lymphocytes against mesenchymal glioblastoma cells. Clin. Can. Res. accepted

Fleurence J, Bahri M, Fougeray S, Faraj S, Vermeulen S, Pinault E, Geraldo F, Oliver L, Véziers J, Marquet P, Rabé M, Gratas C, Vallette F, Pecqueur C, Paris F, Birklé S. Impairing temozolomide resistance driven by glioma stem-like cells with adjuvant immunotherapy targeting O-acetyl GD2 ganglioside. Int J Cancer. (2019) INSERM-02168202

Bahri M, Fleurence J, Faraj S, Ben Mostefa Daho M, Fougeray S, Birklé S. Potentiation of Anticancer Antibody Efficacy by Antineoplastic Drugs: Detection of Antibody-drug Synergism Using the Combination Index Equation. J Vis Exp. (2019) INSERM-01958827

Faraj S, Bahri M, Fougeray S, El Roz A, Fleurence J, Véziers J, Leclair MD, Thébaud E, Paris F, Birklé S. Neuroblastoma chemotherapy can be augmented by immunotargeting O-acetyl-GD2 tumor-associated ganglioside. Oncoimmunology. (2017) INSERM-01596068

Jarry U, Joalland N, Chauvin C, Clemenceau B, Pecqueur C, Scotet E. Stereotactic Adoptive Transfer of Cytotoxic Immune Cells in Murine Models of Orthotopic Human Glioblastoma Multiforme Xenografts. J Vis Exp. (2018) >INSERM-01888508

Oizel K, Chauvin C, Oliver L, Gratas C, Geraldo F, Jarry U, Scotet E, Rabe M, Alves-Guerra MC, Teusan R, Gautier F, Loussouarn D, Compan V, Martinou JC, Vallette FM, Pecqueur C. Efficient Mitochondrial Glutamine Targeting Prevails Over Glioblastoma Metabolic Plasticity. Clin Cancer Res. (2017) INSERM-01596068

Lafargue A, Degorre C, Corre I, Alves-Guerra MC, Gaugler MH, Vallette F, Pecqueur C, Paris F. Ionizing radiation induces long-term senescence in endothelial cells through mitochondrial respiratory complex II dysfunction and superoxide generation. Free Radic Biol Med. (2017) INSERM-01514403

Paul-Gilloteaux P, Potiron V, Delpon G, Supiot S, Chiavassa S, Paris F, Costes SV. Optimizing radiotherapy protocols using computer automata to model tumour cell death as a function of oxygen diffusion processes. Sci Rep. (2017) INSERM-01550008

Niaudet C, Bonnaud S, Guillonneau M, Gouard S, Gaugler MH, Dutoit S, Ripoche N, Dubois N, Trichet V, Corre I, Paris F. Plasma membrane reorganization links acid sphingomyelinase/ceramide to p38 MAPK pathways in endothelial cells apoptosis. Cell Signal. (2017) INSERM-01464136

Fleurence J, Fougeray S, Bahri M, Cochonneau D, Clémenceau B, Paris F, Heczey A, Birklé S. Targeting O-Acetyl-GD2 Ganglioside for Cancer Immunotherapy. J Immunol Res. (2017) INSERM-01474322

Guillonneau M, Paris F, Dutoit S, Estephan H, Bénéteau E, Huot J, Corre I. Oxidative stress disassembles the p38/NPM/PP2A complex, which leads to modulation of nucleophosmin-mediated signaling to DNA damage response. FASEB J. (2016) INSERM-01312779

Jarry U, Chauvin C, Joalland N, Léger A, Minault S, Robard M, Bonneville M, Oliver L, Vallette FM, Vié H, Pecqueur C, Scotet E. Stereotaxic administrations of allogeneic human Vγ9Vδ2 T cells efficiently control the development of human glioblastoma brain tumors. Oncoimmunology. (2016) INSERM-01342603

Fleurence J, Cochonneau D, Fougeray S, Oliver L, Geraldo F, Terme M, Dorvillius M, Loussouarn D, Vallette F, Paris F, Birklé S. Targeting and killing glioblastoma with monoclonal antibody to O-acetyl GD2 ganglioside. Oncotarget. (2016) INSERM-01319327

Dubois N, Rio E, Ripoche N, Ferchaud-Roucher V, Gaugler MH, Campion L, Krempf M, Carrie C, Mahé M, Mirabel X, Paris F. Plasma ceramide, a real-time predictive marker of pulmonary and hepatic metastases response to stereotactic body radiation therapy combined with irinotecan. Radiother Oncol. (2016) INSERM-01333878

Potiron V, Clément-Colmou K, Jouglar E, Pietri M, Chiavassa S, Delpon G, Paris F, Supiot S. Tumor vasculature remodeling by radiation therapy increases doxorubicin distribution and efficacy. Cancer Lett. (2019)

Noblet C, Delpon G, Supiot S, Potiron V, Paris F, Chiavassa S. A new tissue segmentation method to calculate 3D dose in small animal radiation therapy. Radiat Oncol. (2018) INSERM-01812710

Noblet C, Chiavassa S, Smekens F, Sarrut D, Passal V, Suhard J, Lisbona A, Paris F, Delpon G. Validation of fast Monte Carlo dose calculation in small animal radiotherapy with EBT3 radiochromic films. Phys Med Biol. (2016) INSERM-01321438

Revues

Garnier D, Renoult O, Alves-Guerra MC, Paris F, Pecqueur C. Glioblastoma Stem-Like Cells, Metabolic Strategy to Kill a Challenging Target. Front Oncol. (2019)

Corre I, Paris F, Huot J. The p38 pathway, a major pleiotropic cascade that transduces stress and metastatic signals in endothelial cells. Oncotarget. (2017) INSERM-01550120

Collaborations

Silva V, Lafont F, Benhelli-Mokrani H, LeBreton M, Hulin P, Chabot T, Paris F, Sakanyan V, Fleury F. Rapid diminution in the level and activity of DNA-dependent protein kinase in cancer cells by a reactive nitro-benzoxadiazole compound. Int. J. Mol Sciences. (2016) INSERM-01321466

Supiot S, Rousseau C, Dore M, Chèze-Le-Rest C, Kandel-Aznar C, Potiron V, Guerif S, Paris F, Ferrer L, Campion L, Meingan P, Delpon G, Hatt M, Visvikis D. Reoxygenation during radiotherapy in intermediate-risk prostate cancer. Radiother Oncol. (2019)

Supiot S, Rousseau C, Dore M, Cheze-Le-Rest C, Kandel-Aznar C, Potiron V, Guerif S, Paris F, Ferrer L, Campion L, Meingan P, Delpon G, Hatt M, Visvikis D. Evaluation of tumor hypoxia prior to radiotherapy in intermediate-risk prostate cancer using (18)F-fluoromisonidazole PET/CT: a pilot study. Oncotarget. (2018) INSERM-01823478