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Journal articles
APC germline hepatoblastomas demonstrate cisplatin-induced intratumor tertiary lymphoid structures
Guillaume Morcrette
1, 2, 3
Theo Hirsch
1, 2
Elise Badour
4
Jill Pilet
1, 2
Stefano Caruso
1, 2
Julien Calderaro
1, 2, 5, 6
Yoann Martin
1, 2
Sandrine Imbeaud
1, 2
Eric Letouzé
1, 2
Sandra Rebouissou
1, 2
Sophie Branchereau
7
Sophie Taque
8
Christophe Chardot
9
Catherine Guettier
10
Jean-Yves Scoazec
11
Monique Fabre
12
Laurence Brugières
13
Jessica Zucman-Rossi
1, 2, 14
3
EA_3102 - Pathologie pédiatrique
Hôpital Robert Debré, UPD7 - Université Paris Diderot - Paris 7 : EA3102, IFR02
Guillaume Morcrette 1, 2, 3
Author
Theo Hirsch 1, 2
Author
Elise Badour 4
Author
Jill Pilet 1, 2
Author
Stefano Caruso 1, 2
Author
Julien Calderaro 1, 2, 5, 6
Author
Yoann Martin 1, 2
Author
Sandrine Imbeaud 1, 2
Author
Eric Letouzé 1, 2
Author
Sandra Rebouissou 1, 2
Mail :
Author
Sophie Branchereau 7
Author
Sophie Taque 8
Author
Christophe Chardot 9
Author
Catherine Guettier 10
Author
Jean-Yves Scoazec 11
Author
Monique Fabre 12
Mail :
Author
Laurence Brugières 13
Author
Jessica Zucman-Rossi 1, 2, 14
Mail :
Author IdHAL : jessica-zucman-rossi ResearcherId : http://www.researcherid.com/rid/B-5098-2009 ORCID : https://orcid.org/0000-0002-5687-0334
1
CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers (15 rue de l'Ecole de Médecine - Bâtiment B -
75270 Paris Cedex 06 - France)
- EPHE - École pratique des hautes études (4-14 Rue Ferrus, 75014 Paris - France)
- UPD7 - Université Paris Diderot - Paris 7 : UMR_S_1138 (5 rue Thomas-Mann - 75205 Paris cedex 13 - France)
- UPD5 - Université Paris Descartes - Paris 5 : UMR_S_1138 (12, rue de l'École de Médecine - 75270 Paris cedex 06 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1138 (101, rue de Tolbiac, 75013 Paris - France)
- SU - Sorbonne Université (21 rue de l’École de médecine - 75006 Paris - France)
2
Labex OncoImmunology, Equipe labellisée Ligue Contre le Cancer (France)
- UPD5 - Université Paris Descartes - Paris 5 (12, rue de l'École de Médecine - 75270 Paris cedex 06 - France)
3
EA_3102 - Pathologie pédiatrique (48 boulevard Sérurier 75019 Paris - France)
- Hôpital Robert Debré (France)
- UPD7 - Université Paris Diderot - Paris 7 : EA3102 (5 rue Thomas-Mann - 75205 Paris cedex 13 - France)
- IFR02 (France)
4
Service de pédiatrie [CH de la Côte Basque, Bayonne] (France)
- Le CHCB, Centre Hospitalier de la Côte Basque (13 Avenue Jacques Loeb BP 8, 64109 Bayonne Cedex - France)
5
Service d'Anatomopathologie [Hôpital Henri Mondor - APHP] (France)
- CHU Henri Mondor (Créteil - France)
6
IMRB - Institut Mondor de Recherche Biomédicale (8 rue du Général Sarrail 94010 Créteil - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U955 (101, rue de Tolbiac, 75013 Paris - France)
- IFR10 (France)
- UPEC UP12 - Université Paris-Est Créteil Val-de-Marne - Paris 12 : UMR955 (61 avenue du Général de Gaulle - 94010 Créteil cedex - France)
7
Service de chirurgie pédiatrique [Hôpital Bicêtre - APHP] (Le Kremlin Bicetre - France)
- AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre) (78 Rue du Général Leclerc 94270 Le Kremlin-Bicêtre - France)
- Université Paris Saclay (COmUE) (Espace Technologique, Bât. Discovery - RD 128 - 2è ététage, 91190 Saint-Aubin - France)
8
Département de Médecine de l’Enfant et l’Adolescent [CHU de Rennes] (France)
- Centre Hospitalier Universitaire [Rennes] (rue H. Le Guillou 35033 Rennes - France)
9
Service de Chirurgie Viscérale Pédiatrique [Hôpital Necker-Enfants malades - APHP] (149 Rue de Sèvres, 75015 Paris - France)
- APHP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
- CHU Necker - Enfants Malades [AP-HP] (149 Rue de Sèvres 75015 Paris - France)
10
Service d’anatomie et de cytologie pathologiques [Hôpital le Kremlin Bicêtre - APHP] (France)
- UP11 UFR Médecine - Université Paris-Sud 11 - Faculté de médecine (63, rue Gabriel Péri - 94276 Le Kremlin-Bicêtre cedex - France)
- AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre) (78 Rue du Général Leclerc 94270 Le Kremlin-Bicêtre - France)
11
Service d’anatomie et de cytologie pathologiques [Gustave Roussy, Villejuif] (France)
- IGR - Institut Gustave Roussy (114, rue Édouard-Vaillant 94805 Villejuif Cedex -France - France)
12
Service d'anatomie pathologique [CHU Necker] (149 Rue de Sèvres, 75015 Paris - France)
- APHP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
- CHU Necker - Enfants Malades [AP-HP] (149 Rue de Sèvres 75015 Paris - France)
13
Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy] (France)
- IGR - Institut Gustave Roussy (114, rue Édouard-Vaillant 94805 Villejuif Cedex -France - France)
14
Département de cancérologie [Hôpital Européen Georges Pompidou - APHP] (France)
- HEGP - Hôpital Européen Georges Pompidou [APHP] (20, rue Leblanc, 75015 Paris - France)
Abstract : Hepatoblastoma (HB) is the most common liver cancer in children. We aimed to characterize HB related to APC (Adenomatous Polyposis Coli) germline mutation (APC-HB). This French multicentric retrospective study included 12 APC-HB patients under 5 at diagnosis. Clinical features of APC-HB were compared to the French SIOPEL2-3 cohort of HB patients. Molecular and histopathological analyses of APC-HB were compared to 15 consecutive sporadic HB treated at Bicêtre hospital from 2013 to 2015 (non-APC-HB). APC-HB patients have a peculiar spectrum of germline APC mutations, with no events in the main hotspot of classical APC mutations at codon 1309 (P < .05). Compared to sporadic HB, they have similar clinical features including good prognosis since all patients are alive in complete remission at last follow-up. APC-HB are mostly well-limited tumors with fetal predominance and few mesenchymal components. All APC-HB have an activated Wnt/β-catenin pathway without CTNNB1 mutation, confirming that germline APC and somatic CTNNB1 mutations are mutually exclusive (P < .001). Pathological reviewing identified massive intratumor tertiary lymphoid structures (TLS) containing both lymphocytes and antigen-presenting cells in all 11 APC-HB cases who received cisplatin-based neoadjuvant chemotherapy but not in five pre-chemotherapy samples (four paired biopsies and one patient resected without chemotherapy), indicating that these TLS are induced by chemotherapy (P < .001). Conclusion: APC-HB show a good prognosis, they are all infiltrated by cisplatin-induced TLS, a feature only retrieved in a minority of non-APC-HB. This suggests that APC inactivation can synergize with cisplatin to induce an immunogenic cell death that initiates an anti-tumor immune response.
Document type :
Journal articles
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https://www.hal.inserm.fr/inserm-02346879
Contributor : Theo Hirsch <>
Submitted on : Tuesday, November 5, 2019 - 10:14:17 AM
Last modification on : Thursday, June 25, 2020 - 1:54:02 PM
Document(s) archivé(s) le : Thursday, February 6, 2020 - 3:16:11 PM
Contributor : Theo Hirsch <>
Submitted on : Tuesday, November 5, 2019 - 10:14:17 AM
Last modification on : Thursday, June 25, 2020 - 1:54:02 PM
Document(s) archivé(s) le : Thursday, February 6, 2020 - 3:16:11 PM
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OncoimmunologyMorcrette2019.pd...
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Identifiers
- HAL Id : inserm-02346879, version 1
- DOI : 10.1080/2162402X.2019.1583547
- PUBMED : 31069152
Collections
IMRB | UPEC-UPEM | UPEC | FNCLCC | UNIV-PARIS5 | SORBONNE-UNIVERSITE | UNIV-PARIS7 | CORDELIERS | EPHE | PSL | USPC | UNIV-PARIS-SACLAY | SU-SCIENCES | IGR | UP-SANTE
Citation
Guillaume Morcrette, Theo Hirsch, Elise Badour, Jill Pilet, Stefano Caruso, et al.. APC germline hepatoblastomas demonstrate cisplatin-induced intratumor tertiary lymphoid structures. OncoImmunology, Taylor & Francis, 2019, 8 (6), pp.e1583547. ⟨10.1080/2162402X.2019.1583547⟩. ⟨inserm-02346879⟩
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