Immunologic constant of rejection signature is prognostic in soft-tissue sarcoma and refines the CINSARC signature.

Autor:	Bertucci F; Laboratory of Predictive Oncology, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli-Calmettes, Aix-Marseille Université, INSERM UMR1068, CNRS UMR725, Marseille, France bertuccif@ipc.unicancer.fr.; Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France.; French Sarcoma Group, Lyon, France., Niziers V; Laboratory of Predictive Oncology, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli-Calmettes, Aix-Marseille Université, INSERM UMR1068, CNRS UMR725, Marseille, France.; Department of Surgery, Institut Paoli-Calmettes, Marseille, France., de Nonneville A; Laboratory of Predictive Oncology, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli-Calmettes, Aix-Marseille Université, INSERM UMR1068, CNRS UMR725, Marseille, France.; Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France., Finetti P; Laboratory of Predictive Oncology, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli-Calmettes, Aix-Marseille Université, INSERM UMR1068, CNRS UMR725, Marseille, France., Mescam L; French Sarcoma Group, Lyon, France.; Department of Pathology, Institut Paoli-Calmettes, Marseille, France., Mir O; French Sarcoma Group, Lyon, France.; Department of Medical Oncology, Gustave Roussy, Villejuif, France., Italiano A; French Sarcoma Group, Lyon, France.; Department of Medical Oncology, Institut Bergonie, Bordeaux, France., Le Cesne A; French Sarcoma Group, Lyon, France.; Department of Medical Oncology, Gustave Roussy, Villejuif, France., Blay JY; French Sarcoma Group, Lyon, France.; Department of Medical Oncology, Centre Leon Berard, Lyon, France., Ceccarelli M; DIETI, University of Naples Federico II Faculty of Engineering, Naples, Italy., Bedognetti D; Cancer Research, Sidra Medicine, Doha, Qatar.; Department of Internal Medicine and Medical Specialties, University of Genova, Genova, Italy., Birnbaum D; Laboratory of Predictive Oncology, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli-Calmettes, Aix-Marseille Université, INSERM UMR1068, CNRS UMR725, Marseille, France., Mamessier E; Laboratory of Predictive Oncology, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli-Calmettes, Aix-Marseille Université, INSERM UMR1068, CNRS UMR725, Marseille, France.
Jazyk:	angličtina
Zdroj:	Journal for immunotherapy of cancer [J Immunother Cancer] 2022 Jan; Vol. 10 (1).
DOI:	10.1136/jitc-2021-003687
Abstrakt:	Background: Soft-tissue sarcomas (STSs) are heterogeneous and aggressive tumors, with high metastatic risk. The immunologic constant of rejection (ICR) 20-gene signature is a signature of cytotoxic immune response. We hypothesized that ICR might improve the prognostic assessment of early-stage STS. Methods: We retrospectively applied ICR to 1455 non-metastatic STS and searched for correlations between ICR classes and clinicopathological and biological variables, including metastasis-free survival (MFS). Results: Thirty-four per cent of tumors were classified as ICR1, 27% ICR2, 24% ICR3, and 15% ICR4. These classes were associated with patients' age, pathological type, and tumor depth, and an enrichment from ICR1 to ICR4 of quantitative/qualitative scores of immune response. ICR1 class was associated with a 59% increased risk of metastatic relapse when compared with ICR2-4 class. In multivariate analysis, ICR classification remained associated with MFS, as well as pathological type and Complexity Index in Sarcomas (CINSARC) classification, suggesting independent prognostic value. A prognostic clinicogenomic model, including the three variables, was built in a learning set (n=339) and validated in an independent set (n=339), showing greater prognostic precision than each variable alone or in doublet. Finally, connectivity mapping analysis identified drug classes potentially able to reverse the expression profile of poor-prognosis tumors, such as chemotherapy and targeted therapies. Conclusion: ICR signature is independently associated with postoperative MFS in early-stage STS, independently from other prognostic features, including CINSARC. We built a robust prognostic clinicogenomic model integrating ICR, CINSARC, and pathological type, and suggested differential vulnerability of each prognostic group to different systemic therapies. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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