학술논문
Upregulation of intratumoral HLA class I and peritumoral Mx1 in ulcerated melanomas.
Document Type
Academic Journal
Author
Verver D; Department of Surgical Oncology, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, Rotterdam, The Netherlands.; Poirier-Colame V; Department of Immuno-Oncology, Gustave Roussy Cancer Campus Grand Paris, Villejuif, France.; Tomasic G; Department of Pathology, Gustave Roussy Cancer Campus Grand Paris, Villejuif, France.; Cherif-Rebai K; Department of Pathology, Gustave Roussy Cancer Campus Grand Paris, Villejuif, France.; Grunhagen DJ; Department of Surgical Oncology, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, Rotterdam, The Netherlands.; Verhoef C; Department of Surgical Oncology, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, Rotterdam, The Netherlands.; Suciu S; Department of Biostatistics, European Organisation for Research and Treatment of Cancer Headquarters, Brussels, Belgium.; Robert C; Department of Medicine, Service of Dermatology Gustave Roussy and University Paris-Sud.; Zitvogel L; INSERM U 1015, Gustave Roussy Cancer Campus Grand Paris, Villejuif, France.; Eggermont AMM; INSERM U 1015, Gustave Roussy Cancer Campus Grand Paris, Villejuif, France.; University Paris-Sud, Le Kremlin Bicetre, France.
Source
Publisher: Taylor & Francis Country of Publication: United States NLM ID: 101570526 Publication Model: eCollection Cited Medium: Print ISSN: 2162-4011 (Print) Linking ISSN: 21624011 NLM ISO Abbreviation: Oncoimmunology Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
2162-4011
Abstract
Before the era of immune checkpoint blockade, a meta-analysis encompassing fifteen trials reported that adjuvant IFN-α significantly reduces the risk of relapse and improves survival of ulcerated melanoma (UM) with no benefit for higher doses compared to lower doses. IFNa2b affects many cell intrinsic features of tumor cells and modulates the host innate and cognate immune responses. To better understand the biological traits associated with ulceration that could explain the efficacy of prophylactic type 1 IFN, we performed immunohistochemical analysis of various molecules (major histocompatibility complex class I and class II, MX Dynamin Like GTPase 1 (MX1), inducible Nitric-Oxide Synthase (iNOS) or CD47) in two retrospective cohorts of melanoma patients, one diagnosed with a primary cutaneous melanoma (1995-2013, N = 172, among whom 49% were ulcerated melanoma (UM)) and a second one diagnosed with metastatic melanoma amenable to lymph node resection (EORTC 18952 and 18991 trials, N = 98, among whom 44% were UM). We found that primary and metastatic UM exhibit higher basal expression of MHC class I molecules, independently of Breslow thickness, histology and lymphocytic infiltration compared with NUM and that primary UM harbored higher constitutive levels of the antiviral protein Mx1 at the border of tumor beds than NUM. These findings suggest that UM expand in a tumor microenvironment where chronic exposure to type 1 IFN could favor a response to exogenous IFNs.
(© 2019 Taylor & Francis Group, LLC.)
(© 2019 Taylor & Francis Group, LLC.)