APC germline hepatoblastomas demonstrate cisplatin-induced intratumor tertiary lymphoid structures

Guillaume Morcrette, Theo Z. Hirsch, Elise Badour, Jill Pilet, Stefano Caruso, Julien Calderaro, Yoann Martin, Sandrine Imbeaud, Eric Letouzé, Sandra Rebouissou, Sophie Branchereau, Sophie Taque, Christophe Chardot, Catherine Guettier, Jean Yves Scoazec, Monique Fabre, Laurence Brugières, Jessica Zucman-Rossi

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

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    Résumé

    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.

    langue originaleAnglais
    Numéro d'articlee1583547
    journalOncoImmunology
    Volume8
    Numéro de publication6
    Les DOIs
    étatPublié - 3 juin 2019

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