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UMR 9018 - Team 2 - « Host-tumor interactions in Head and Neck Carcinomas »


Academic year: 2021

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UMR 9018- Team 2

« Host-tumor interactions in Head and Neck Carcinomas »

(Pierre Busson / Karim Benihoud)

Composition de l’équipe

Pierre Busson, DR1 responsable de l’équipe

Karim Benihoud, PR1 Paris Saclay, co-responsable de l’équipe

Thierry Ragot, CRCN

Léna Zig, AI

Aurore Gelin, TCS

Tram Thi Bao Tran, doctorante

Salomé Laurans, doctorante

François Moreau, IE

Sarah Awan Toor, IE

Ingrid Breuskin, chirurgie ORL

Philippe Gorphe, chirurgie ORL

Caroline Even, oncologie médicale Cliniciens rattachés à l’équipe

General background

Public health problem

Exposure to carcinogens (tobacco, alcohol, …)

Possible etiologic contributions of viruses e.g. Human PapillomaVirus

Systemic diseases :

Multiple factors of immune escape

Cachexia and muscle wasting Institutional context

Excellent medical performances at Gustave Roussy

Previous collaborations on nasopharyngeal carcinomas

A need for broader projects in basic and translational research

Main characteristics of Head and Neck carcinomas (HNCs)

Immunological aspects:

Objective responses to anti-PD1/PD-L1 in 15%- 20% cases

50% of patients non-eligible because of cachexia

Mechanisms of primary and secondary resistances under investigation

High prevalence of cachexia

Immunological and metabolic aspects of HNCs

Two approaches against tumor immune suppression:

Neutralisation of suppressive factors in the tumor microenvironment (focus on extra-cellular galectin-9)

Stimulation of the immune response against tumor antigens (vaccination using recombinant adenoviruses)

Extra-cellular galectin-9 and HNCs

Recent achievements

Obtention and characterization of murine tumor models KO for Gal-9

(Baloche et al., under revision in Scientific Reports)

Patent on antibodies neutralizing extra-cellular galectin-9 licensed to HifiBiO Therapeutics since February 2017

Gal-9L Gal-9M

actin Days

Sub-cutaneous injection of MB49 cells


0 20 40 60

2ndcycle 3rdcycle

Serial transplantation of tumor fragments

1 1


2 3

3 4



Characterization of human T-lymphocytes resistant to apoptosis induced by gal-9

Investigations on plasma gal-9 in HNC patients with primary or secondary resistances to anti-PD1/PD-L1

Staff: P. Busson, A. Gelin, T. Thi Bao Tram

Funding: HiFiBiO Therapeutics, current application to Unicancer

Galectin-9 and HNCs: ongoing projects Galectin-9 and HNCs: collaborations

Jiang Li, Sun Yat-Sen University Cancer Center, Canton

Udo Kontny, Uniklinik RWTH, université d’Aix la Chapelle

Olivier Dellis, Inserm UMR 1174, université Paris-Saclay

Nao Yamagawa, plateforme PAGés, UMR 8576, univ. de Lille

Nadira Delhem and Olivier Morales, Inst. de Biologie de Lille

Adenoviral vaccinations

Successfull mouse immunisation against HPV L2 or E6/E7 using epitope display on adenovirus capsid (Ramdani et al. in preparation)

Induction of humoral and cellular responses against a model antigen using protein display on bacteriophage T5 capsid (Ramdani et al. in preparation, patent deposit PCT/FR2020/051628)

Recent achievements (ongoing publications)


(12 x 3 copies)

Epitope display Protein display

pb10 (120 copies) Hexon

(240 x 3 copies)

Adenoviral plateform WO 2012/150478

Phage T5 plateform PCT/FR2020/051628 Collaboration P. Boulanger

Vaccination plateforms Adenoviral vaccinations: ongoing projects

Development of adenovirus vectors and oncolytic adenoviruses targeting HNCs

Characterization of adenovirus interaction with blood components

In situ vaccination with oncolytic adenoviruses

Staff: K. Benihoud, L. Zig, F. Moreau, S. Laurans Funding: ANR

Adenovirus: collaborations

Pierre Bobé, équipe Immunorégulation, Chimiokines et Persistance Virale , INSERM UMR 996, Clamart

Pascale Boulanger, équipe Bactériophage T5, Institut de biologie intégrative de la cellule (I2BC), CNRS UMR , Orsay

Sophie Dupré, laboratoire chimie physique, CNRS UMR 8000, Orsay

Anja Ehrhardt, Witten university, Witten, Germany

Pascal Fender, équipe Adénovirus, Institut de biologie structurale, Grenoble

Combination of adenoviral transduction and electro- permeabilisation

Other projects

Viral particles Metal particles

« Metallic particles generated during millisecond pulse

application enhance adenovirus-mediated gene transfer in CAR-negative cells »

Close to submission

Thierry Ragot CRCN CNRS

Novel therapeutic approaches for EBV associated malignancies

Collaboration with T. Messick (Wistar Institute and Cullinan Oncology)

NCT03682055 - VK 2019 anti-EBNA1 small molecules on trial in

various centers including Gustave Roussy (Caroline Even, Clémentine Sarkozy, Jean-Marie Michot)

Collaboration with Viracta Therapeutics on a compound inducing EBV lytic cycle in NPC cells

Manuscript in preparation

Caroline Even, oncologue médicale

Functional genomics of cachexia and sarcopenia in HNCs

Collection of muscle fragments


Metabolic profile Epigenetic profile

Correlations with clinical observations and outcome ?

Confirmation of c-IAP2 overexpression ?

Ancillary study of Magnolia (ongoing PHRC)

General aim :

to take advantage of reconstructive surgery for exploration of muscle alterations in situ

Pilot study performed by H. Hachicha (DUERTECC – 2018/2019)

Abstract submitted to AACR 2021 : « Cellular and molecular

alterations of sarcopenic muscles in Head and Neck carcinomas » Philippe Gorphe, chirurgien ORL


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