CSF1R Protein Expression in Reactive Lymphoid Tissues and Lymphoma: Its Relevance in Classical Hodgkin Lymphoma

• Published in: PloS one Vol. 10; no. 6; p. e0125203
• Main Authors: Martín-Moreno, Ana M, Roncador, Giovanna, Maestre, Lorena, Mata, Elena, Jiménez, Scherezade, Martínez-Torrecuadrada, Jorge L, Reyes-García, Ana I, Rubio, Carmen, Tomás, José F, Estévez, Mónica, Pulford, Karen, Piris, Miguel A, García, Juan F
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.06.2015; Public Library of Science (PLoS)
• Subjects: Anaplastic large-cell lymphoma; Angiogenesis; Animals; B-cell lymphoma; Cancer; CD163 antigen; Cell Line, Tumor; Cell survival; Clinical outcomes; Cloning; Colony-stimulating factor; Cytokines; Deactivation; Gene Expression; Hematology; Hodgkin Disease - genetics; Hodgkin Disease - metabolism; Hodgkin Disease - pathology; Hodgkin's disease; Hodgkin's lymphoma; Humans; Immunoglobulins; Immunohistochemistry; Immunoprecipitation; Inactivation; Kinases; Leukemia; Lymphocytes B; Lymphocytes T; Lymphoid tissue; Lymphoid Tissue - metabolism; Lymphoid Tissue - pathology; Lymphoma; Lymphoma - diagnosis; Lymphoma - genetics; Lymphoma - metabolism; Macrophage colony-stimulating factor; Macrophages; Medical prognosis; Metastasis; Mice; Monoclonal antibodies; Pathology; Patients; Protein expression; Proteins; Receptor, Macrophage Colony-Stimulating Factor - genetics; Receptor, Macrophage Colony-Stimulating Factor - metabolism; Signal Transduction; Survival; T-cell lymphoma; Therapeutic applications; Tissues; Tumors; Spain
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0125203

Tumour-associated macrophages (TAMs) have been associated with survival in classic Hodgkin lymphoma (cHL) and other lymphoma types. The maturation and differentiation of tissue macrophages depends upon interactions between colony-stimulating factor 1 receptor (CSF1R) and its ligands. There remains, however, a lack of consistent information on CSF1R expression in TAMs. A new monoclonal antibody, FER216, was generated to investigate CSF1R protein distribution in formalin fixed tissue samples from 24 reactive lymphoid tissues and 187 different lymphoma types. We also analysed the distribution of CSF1R+, CD68+ and CD163+ macrophages by double immunostaining, and studied the relationship between CSF1R expression and survival in an independent series of 249 cHL patients. CSF1R+ TAMs were less frequent in B-cell lymphocytic leukaemia and lymphoblastic B-cell lymphoma than in diffuse large B-cell lymphoma, peripheral T-cell lymphoma, angioimmunoblastic T-cell lymphoma and cHL. HRS cells in cHL and, with the exception of three cases of anaplastic large cell lymphoma, the neoplastic cells in NHLs, lacked detectable CSF1R protein. A CSF1R+ enriched microenvironment in cHL was associated with shorter survival in an independent series of 249 cHL patients. CSF1R pathway activation was evident in the cHL and inactivation of this pathway could be a potential therapeutic target in cHL cases.