Analysis of microenvironment of peripheral T-cell lymphoma, not otherwise specified

• Project/Area Number: 20K16204
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Aichi Medical University
• Principal Investigator: Satou Akira 愛知医科大学, 医学部, 講師 (40732699)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2020: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 末梢性T細胞リンパ腫、非特定型 / Lymphoepithelioid type / 組織球 / CD30免疫染色 / 末梢性T細胞リンパ腫，非特定型 / 末梢性T細胞性リンパ腫, 非特定型 / 微小環境 / RNAscope / サイトカイン

Outline of Research at the Start

近年、種々のがんにおいて、その腫瘍細胞周囲の微小環境ががんの生物学的特徴を決定する上で重要な役割を担っていることが明らかにされてきた。しかしながらPTCL-NOSでは、微小環境の解析が進んでおらず、未だ明らかにされていない部分が多い。
我々はPTCL-NOSの微小環境中のサイトカインに着目し、RNAscopeを用いることで微小環境におけるサイトカインの多寡、分布を解析する。その結果を用いて、PTCL-NOSの臨床病理学的解析を行う。これらを通じてPTCL-NOSの微小環境におけるサイトカインの役割を明らかにし、PTCL-NOSの病因・病態を解明する。

Outline of Final Research Achievements

Due to the rarity and overlapping histological features, the boundary between angioimmunoblastic T-cell lymphoma with high content of epithelioid cells (AITL-EPI) and Lennert lymphoma (LeL) is still obscure. We performed comparative analysis and found that LeL had significantly better prognosis than AITL-EPI. We tested for CD68 and CD163 expression in these two entities; all of the tested cases expressed CD68 on epithelioid histiocytes, whereas CD163 expression was detected only in AITL-EPI. The frequency of CD163 positivity between AITL-EPI(33%) and LeL(0%) showed significant difference. These results suggest that M1 macrophage-rich tumor microenvironment contribute to the favorable prognosis of LeL.
We also analyzed 60 cases of PTCLs for equalization of CD30 immunohistochemistry. We revealed that following conditions for each autostainer are suitable for equal CD30 immunohistochemistry: Ventana(OptiView)、Bond III(dilution 1:200-400)、Dako Omnis(with linker、dilution 1:100-200).

Academic Significance and Societal Importance of the Research Achievements

PTCL-NOSの稀な亜型であるLeLとAITL-EPIの予後、微小環境中の組織球の性質の違いを明らかにした。両者は組織学的に類似していることもあり、鑑別が問題となるが、診断時に両者を厳密に区別することが重要であり、またPTCLの微小環境が腫瘍の性質に影響を与えるということが分かった。
CD30免疫染色はPTCL患者にBrentuximab vedotinの使用を決定する上でCD30免疫染色による検索は必須事項となっている。各社の自動免疫染色装置によるCD30免疫染色を均てん化することはPTCL患者におけるBrentuximab vedotinの適正使用に繋がることが期待される。

Research Products

• [Journal Article] Pathological and Molecular Features of Nodal Peripheral T-Cell Lymphomas (2022)
  • Author(s): Satou Akira、Takahara Taishi、Tsuzuki Toyonori
  • Journal Title: Diagnostics Volume: 12 Issue: 8 Pages: 2001-2001
  • DOI: 10.3390/diagnostics12082001
• [Journal Article] Hodgkin Lymphoma: Biology and Differential Diagnostic Problem (2022)
  • Author(s): Takahara Taishi、Satou Akira、Tsuzuki Toyonori、Nakamura Shigeo
  • Journal Title: Diagnostics Volume: 12 Issue: 6 Pages: 1507-1507
  • DOI: 10.3390/diagnostics12061507
• [Journal Article] EBV‐positive B‐cell lymphomas and lymphoproliferative disorders: Review from the perspective of immune escape and immunodeficiency (2021)
  • Author(s): Satou Akira、Nakamura Shigeo
  • Journal Title: Cancer Medicine Volume: 10 Issue: 19 Pages: 6777-6785
  • DOI: 10.1002/cam4.4198
  • Peer Reviewed / Open Access
• [Journal Article] The Positivity of Phosphorylated STAT3 Is a Novel Marker for Favorable Prognosis in Germinal Center B-Cell Type of Diffuse Large B-Cell Lymphoma (2021)
  • Author(s): K. Morichika, K. Karube, S. Sakihama, R. Watanabe, M. Kawaki, Y. Nishi, S. Nakachi, S. Okamoto, T. Takahara, A. Satou, S. Shimada, K. Shimada, T. Tsuzuki, T. Fukushima, S. Morishima and H. Masuzaki
  • Journal Title: Am J Surg Pathol Volume: - Issue: 6 Pages: 832-840
  • DOI: 10.1097/pas.0000000000001691
  • Peer Reviewed / Open Access
• [Journal Article] Primary cutaneous methotrexate-associated B-cell lymphoproliferative disorders other than EBV-positive mucocutaneous ulcer: clinical, pathological, and immunophenotypic features (2021)
  • Author(s): Satou Akira、Banno Shogo、Kohno Kei、Takahara Taishi、Takahashi Emiko、Nobata Hironobu、Iwagaitsu Shiho、Watanabe Daisuke、Hanamura Ichiro、Takami Akiyoshi、Ito Yasuhiko、Nakamura Shigeo、Tsuzuki Toyonori
  • Journal Title: Pathology Volume: - Issue: 5 Pages: 595-601
  • DOI: 10.1016/j.pathol.2020.10.019
  • Peer Reviewed / Open Access