Colony stimulating factor 1 receptor (CSF1R) and immune regulatory M2c-like tumor associated macrophages (TAMs) in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma transformation (tFL)

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K19061
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human pathology
• Research Institution: Tokai University
• Principal Investigator: CARRERAS Joaquim 東海大学, 医学部, 講師 (90637191)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: CSF1R / びまん性大細胞型B細胞リンパ腫 / 濾胞性リンパ腫 / 腫瘍関連マクロファージ / 血液病理学 / 免疫組織化学 / 全ゲノムのコピー数解析 / CD163

Outline of Final Research Achievements

We successfully analyzed CSF1R [pro-tumoral M2-like tumor associated macrophages(TAMs)], immune regulatory M2c-like TAMs (CD163, PTX3, IL10, TGFB) and other markers of immune microenvironment in Diffuser Large B-cell Lymphoma (DLBCL, 240 cases, 29 sinonasal) and Follicular Lymphoma (FL, 100 Japan, 88 Europe). We performed (1) Immunohistochemistry and digital image quantification (2) Immunofluorescence, optical, confocal and atomic force microscopy (3) Genome-wide copy number and loss-of-heterozygosity (LOH) profiling (4) In vitro analysis of M2 macrophages + FL with gene expression profiling, including GSEA and network analysis (5) Correlation with histological and clinical features. We concluded that high CSF1R and M2c-like markers correlated with FL progression and DLBCL transformation; TAMs created 3D networks, TAMs induced changes in gene expression of immune response type II, high TAMs associated with poor prognosis in DLBCL and TAMs correlated with high copy No changes and RGS1.

Free Research Field

医歯薬学 人体病理学