2016 Fiscal Year Annual Research Report
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)
| Project/Area Number |
15K19061
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| Research Institution | Tokai University |
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Principal Investigator |
カレーラス ジュアキム 東海大学, 医学部, 講師 (90637191)
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| 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 / 全ゲノム解析 / CD163 |
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| Outline of Annual Research Achievements |
We have focused on CSF1R marker, which identifies tumor associated macrophages, as well as a series of associated tumor microenvironment immune biomarkers.In this second year of research we have successfully advanced in the project. The series of cases has expanded, DLBCL (n=240) and FL (n=100) from Japan and FL Europe (n=88). Staining was successful for IL10, TFGB, CCR2, CASP3, CD14, IL17A, CD169, CD204 and RGS1, among others. In DLBCL Japan CSF1R M2-like macrophages associated with poor progression free survival (PFS) (P=0.016). High CD163 with poor overall survival (OS) and PFS (P=0.009 and P=0.005). In FL Europe: (1) High grade FL correlated with high follicular CSF1R (60.7% vs. 5.1%, P<0.0001); (2) High follicular CSF1R had trend correlation to poor OS (P=0.091); (3) High CD163 correlated with higher LDH (P=0.003); (4) COX regression between CSF1R and FLIPI showed only FLIPI significant for PFS. Atomic force microscopy identified connection area between macrophages and B-lymphocytes.In-vitro study of macrophages and FL showed increased gene expression of angiogenesis, matrix degradation of chemokine signaling; GSEA analysis showed increased markers of host immune response type II, including macrophage markers.In sinonasal DLBCL Japan, high macrophages associated to higher genomic copy number changes and RGS1 marker was identified with prognostic relevance. In summary, our results are highlighting the relevance of CSF1R and immune microenvironment biomarkers in the pathogenesis of two of the most frequent non-Hodgkin lymphomas of Western Countries as well as Japan.
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[Journal Article] Clinicopathological characteristics and genomic profile of primary sinonasal tract diffuse large B cell lymphoma (DLBCL) reveals gain at 1q31 and RGS1 encoding protein; high RGS1 immunohistochemical expression associates with poor overall survival in DLBCL not otherwise specified (NOS).2017
Author(s)
Carreras J, Kikuti YY, Bea S, Miyaoka M, Hiraiwa S, Ikoma H, Nagao R, Tomita S, Martin-Garcia D, Salaverria I, Sato A, Ichiki A, Roncador G, Garcia JF, Ando K, Campo E, Nakamura N.
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Journal Title
Histopathology
Volume: 70
Pages: 595-621
DOI
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Presentation] RGS1陽性DLBCLの臨床病理学的特徴とゲノムプロファイル解析2017
Author(s)
Carreras Joaquim, 菊池イアーラ 幸江, 宮岡 雅, 平岩 信一郎, 冨田 さくら, Perez Patricia, Bea Silvia, 安藤 潔, Campo Elias, 中村 直哉
Organizer
第57回日本リンパ網内系学会総会
Place of Presentation
京王プラザホテル 〒160-8330 東京都新宿区西新宿2-2-1
Year and Date
2017-06-29 – 2017-07-01
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