Positive Association Between Location of Melanoma, Ultraviolet Signature, Tumor Mutational Burden, and Response to Anti–PD-1 Therapy
| العنوان: | Positive Association Between Location of Melanoma, Ultraviolet Signature, Tumor Mutational Burden, and Response to Anti–PD-1 Therapy |
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| المؤلفون: | Léa Dousset, Florence Poizeau, Caroline Robert, Sandrine Mansard, Laurent Mortier, Charline Caumont, Émilie Routier, Alain Dupuy, Jacques Rouanet, Maxime Battistella, Anna Greliak, David Cappellen, Marie-Dominique Galibert, Clara Allayous, Alexandra Lespagnol, Émilie Gerard, Inès Kerneuzet, Séverine Roy, Caroline Dutriaux, Jean-Philippe Merlio, Beatrice Vergier, Alexa B. Schrock, Jessica Lee, Siraj M. Ali, Solène-Florence Kammerer-Jacquet, Céleste Lebbé, Marie Beylot-Barry, Lise Boussemart |
| المساهمون: | CHU Bordeaux [Bordeaux], Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), CHU Pontchaillou [Rennes], Institut Gustave Roussy (IGR), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, CHU Lille, Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Foundation Medicine Inc, Institut de recherche en santé, environnement et travail (Irset), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Dupuis, Christine, Service de dermatologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Université Paris-Saclay, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de pathologie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université de Bordeaux (UB), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Foundation Medicine, Inc. [Cambridge, MA, USA], EQRX Inc [Cambridge, MA, USA], Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de Pathologie [Rennes] = Pathology [Rennes], Immunology and New Concepts in ImmunoTherapy (INCIT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ) |
| المصدر: | JCO Precision Oncology JCO precision oncology JCO precision oncology, American Society of Clinical Oncology, 2021, 5, ⟨10.1200/PO.21.00084⟩ JCO precision oncology, 2021, 5 (5), pp.PO.21.00084. ⟨10.1200/PO.21.00084⟩ |
| بيانات النشر: | Wolters Kluwer Health, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Cancer Research, [SDV]Life Sciences [q-bio], Infant, Newborn, ORIGINAL REPORTS, Cumulative sun exposure, B7-H1 Antigen, [SDV] Life Sciences [q-bio], Tumor mutational burden (TMB), Oncology, Child, Preschool, Mutation, Biomarkers, Tumor, Humans, Prospective Studies, Location of the primary melanoma, Precision Medicine, Melanoma |
| الوصف: | PURPOSE Emerging evidence suggests a correlation between the tumor mutational burden (TMB) and the response to programmed cell death-1 protein (PD-1) monotherapy across multiple cancer types. In skin cancers, as high TMB is mostly because of ultraviolet (UV) exposure, we hypothesized a correlation between the primary melanoma cutaneous location according to sun exposure and response to anti–PD-1 monotherapy. METHODS The aim of this study was to analyze, in advanced melanoma, the relationship between TMB, locations according to sun exposure, and response to PD-1 inhibitors. We conducted a prospective multicentric analysis, by sequencing the most recent metastatic sample before PD-1 inhibitors using FoundationOne assay. RESULTS One hundred two patients were included, with TMB available for 94 cases. In univariate and multivariate linear regression, TMB was significantly associated with sun-exposed areas of the primary melanoma location and with age (coefficients of the association with log-TMB: non-UV location, –1.05; chronic sun-exposed area, 1.12; P value for the location, < 10–5; age, 0.021 per year, P value for age, .002). Molecular UV signature present on the metastatic site was associated with higher TMB (P = .003). Melanomas bearing a high TMB had a higher probability of response to PD-1 inhibitors compared with melanomas with a low TMB, with a dose-dependent effect following an exponential curve and a negative odds ratio of 0.40 (95% CI, 0.20 to 0.72, P = .004) between log-TMB and 6-month progression. CONCLUSION Cumulative sun exposure related to skin location and molecular UV signature present on the metastatic site appear to be relevant biomarkers directly linked to TMB. Because TMB is not yet available to all for routine clinical use, the location of the primary melanoma in a sun-exposed area may play an important role in clinical decisions regarding therapeutic choice. The location of the primary melanoma in a sun-exposed area can help choosing first-line advanced melanoma treatment. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2473-4284 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e2710a59cfb32077d16db1c59d0232edTest http://europepmc.org/articles/PMC8691497Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e2710a59cfb32077d16db1c59d0232ed |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 24734284 |
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