• 研究課題をさがす
  • 研究者をさがす
  • KAKENの使い方
  1. 課題ページに戻る

2015 年度 実施状況報告書

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)

研究課題

研究課題/領域番号 15K19061
研究機関東海大学

研究代表者

カレーラス ジュアキム  東海大学, 医学部, 講師 (90637191)

研究期間 (年度) 2015-04-01 – 2017-03-31
キーワードCSF1R / 腫瘍関連マクロファージ / 濾胞性リンパ腫 / びまん性大細胞型B細胞リンパ腫 / 血液病理学 / 免疫組織化学
研究実績の概要

We aimed to elucidate the role of CSF1R and M2-like Tumor Associated Macrophages (TAMs) in de novo Diffuse Large B-cell Lymphoma (DLBCL) and Follicular Lymphoma (FL).
We analyzed CSF1R pathway in 109 cases of de novo DLBCL by immunohistochemical and digital analysis on CSF1R, CSF1, STAT3, NF-KB, MYC and Ki67, including 3D cell marker localization. The markers showed a right-skewed distributions. No correlation was found with most of the clinical variables except for CSF1R. Mean CSF1R expression was 25%±25.3 with bimodal distribution (at 60% cutoff the TAMs vs B cell expression patterns were differentiated). CSF1R conferred prognostic relevance: CSF1R+B cell pattern was associated with favorable prognosis [5 year PFS of 87% (P=0.018); HR of 0.1 (P=0.032)] while CSF1R+TAM pattern to unfavorable prognosis[5 year PFS of 53% (P=0.018); HR of 4.7 (P=0.032)].
We also studied microenvironment markers in DLBCL and FL. FL series was comprised of 26 FL (low grade, 13; high grade 3a, 7; 3b, 3; and transformed FL, 3). Immunohistochemistry focused on pan-TAMs (CD68), M1-like TAMs (CD16), M2-like TAMs (CSF1R, CD163, PTX3, MITF, CCR2 and CSF1) and FOXP3+Tregs.In comparison to DLBCL, FL is characterized by lower expression of CD68, CD16, CD163, MITF and FOXP3 (P<0.05). Progression of FL towards tFL is characterized by progressive increase of CD68, CSF1R, CD163 and MITF (P<0.05).
Of note, sinonasal DLBCL has also been investigated for CSF1R.
In conclusion, CSF1Ris relevant for the prognosis of de novo DLBCL as well as for the FL progression and transformation to DLBCL.

現在までの達成度 (区分)
現在までの達成度 (区分)

2: おおむね順調に進展している

理由

The progress of the project is rather smooth and we have already achieved most of the planned aims.

The immunohistochemistry of some markers of CSF1R pathway such as STAT5, CSF1 and HIF1 are difficult to interpret due to their wide range of expression in different cell populations. The staining for IL10, which is an important immune regulatory marker candidate in our project, is also difficult; so far we have tried 3 different antibody clones but we still fail to identify specific staining in macrophages neither in benign and tumoral lymphoid tissue.

今後の研究の推進方策

1) Increase the number of cases of the series of DLBCL as well as FL in order to increase the power of the statistical analysis. We would like to reach the 200 cases in total for DLBCL and around 100 for FL.

2) Add new markers to be analyzed by immunohistochemistry that may allow to further characterize the CSF1R pathway as well as to subclassify the M2-like TAMs into M2a, M2b and M2c and differentiate from M1 polarization.

3) In vitro analysis with DLBCL cell lines or genomic profile-gene expression of the most characteristic cases associated with unfavorable prognosis.

  • 研究成果

    (2件)

すべて 2016

すべて 学会発表 (2件)

  • [学会発表] Relevance of macrophagic signature in follicular lymphoma (FL), transformation to diffuse large B-cell lymphoma (tFL), and comparison with de novo diffuse large B-cell lymphoma (DLBCL)2016

    • 著者名/発表者名
      カレーラス ジュアキム、菊池 イアーラ幸江、雅宮岡、平岩真一郎、生駒悠、冨田さくら、中村直哉
    • 学会等名
      第56回日本リンパ網内系学会総会
    • 発表場所
      ホテル日航熊本 〒860-8536 熊本市中央区上通町2-1
    • 年月日
      2016-05-19 – 2016-05-21
  • [学会発表] Clinicopathological and genomic profiles of primary de novo sinonasal diffus e large B-cell lymphoma2016

    • 著者名/発表者名
      カレーラス ジュアキム、菊池イアーラ幸江、宮岡雅、平岩真一郎、生駒悠、ベア シールビア、カンポ エリーアス、中村直哉
    • 学会等名
      第105回日本病理学会総会
    • 発表場所
      仙台国際センター 〒980-0856 仙台市青葉区青葉山無番地
    • 年月日
      2016-05-12 – 2016-05-14

URL: 

公開日: 2017-01-06  

サービス概要 検索マニュアル よくある質問 お知らせ 利用規程 科研費による研究の帰属

Powered by NII kakenhi