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Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer
Published on: February 12, 2017
APC germline hepatoblastomas demonstrate cisplatin-induced intratumor tertiary lymphoid structures
Guillaume Morcrette1,2,3, Theo Z Hirsch1,2, Elise Badour4
1Centre de Recherche des Cordeliers, Functional Genomics of Solid Tumors laboratory, Sorbonne Université, Inserm, USPC, Université Paris Descartes, Université Paris Diderot, 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.
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