Strategy of therapy on follicular lymphoma targeting estrogen receptor alpha-positive follicular dendritic cell

• Project/Area Number: 19K16577
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Yamagata University
• Principal Investigator: Ohe Rintaro 山形大学, 医学部, 講師 (40594338)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: estrogen receptor alpha / CD23 / FDC / follicular lymphoma / FLIPI / prognosis / エストロゲン受容体α / 濾胞樹状細胞 / 濾胞性リンパ腫

Outline of Research at the Start

濾胞性リンパ腫は難治性であり、その要因にはリンパ腫細胞自身の増殖能と腫瘍免疫を含む微小環境による腫瘍保護作用の2つの問題がある。標準治療はリンパ腫細胞に対する化学療法であるが、根治に至らない。そこで、微小環境による腫瘍保護作用のメカニズム解明に着目した。
濾胞性リンパ腫の微小環境の根幹をなすリンパ腫関連濾胞樹状細胞に発現するエストロゲン受容体αに焦点を当て、抗エストロゲン療法の濾胞性リンパ腫への応用を目指す。

Outline of Final Research Achievements

The number of estrogen receptor alpha (ERα)-positive cells was found to be lower in axillary lymph nodes after anti-estrogen therapy compared to untreated axillary lymph nodes, and in addition, the area of germinal center, CD21-positive and CD23-positive follicular dendritic cells was smaller.
Within the follicular lymphoma (FL) microenvironment, there were more ERα- and CD23-expressing cells in Grades 1-2 than in Grade 3.
In terms of both overall survival and progression-free survival, FL in the high ERα group had a better prognosis than FL in the low ERα group, and high ERα expression was found to be an independent prognostic factor in FL.

Academic Significance and Societal Importance of the Research Achievements

本研究成果より、抗エストロゲン治療が濾胞樹状細胞（FDC）の増生・増殖を抑えることが出来る可能性があることを見出した。さらに、ER陽性CD23陽性FDCはGrade 1-2の濾胞性リンパ腫（FL）に多く存在し、G3 FLではほとんどみられなかったことより、G3 FLよりもG1-2 FLに抗エストロゲン治療の効果が期待出来る。

Research Products

• [Int'l Joint Research] ハルビン医科大学附属腫瘍医院(中国)
• [Journal Article] Nodal histiocytic sarcoma with prominent eosinophilic infiltration: expression of eotaxin-2 on tumor cells (2021)
  • Author(s): Ohe Rintaro、Kabasawa Takanobu、Utsunomiya Aya、Urano Yuka、Kitaoka Takumi、Suzuki Kazushi、Aung Naing Ye、Kawamura Ichiro、Tajima Katsushi、Ishiyama Tomoharu、Yamakawa Mitsunori
  • Journal Title: Diagnostic Pathology Volume: 16 Issue: 1 Pages: 0-0
  • DOI: 10.1186/s13000-020-01061-4
  • Peer Reviewed / Open Access
• [Journal Article] Potential role of M2 TAMs around lymphatic vessels during lymphatic invasion in papillary thyroid carcinoma (2021)
  • Author(s): Kabasawa Takanobu、Ohe Rintaro、Aung Naing Ye、Urano Yuka、Kitaoka Takumi、Tamazawa Nobuyuki、Utsunomiya Aya、Yamakawa Mitsunori
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 0-0
  • DOI: 10.1038/s41598-020-80694-3
  • Peer Reviewed / Open Access
• [Journal Article] Other Iatrogenic Immunodeficiency-Associated Lymphoproliferative Disorders, Diffuse Large B-Cell Lymphoma Type, in a Patient with Beh?et’s Disease Treated with Cyclosporine A (2020)
  • Author(s): Urano Yuka、Ohe Rintaro、Yamada Akane、Kabasawa Takanobu、Suzuki Kazushi、Kitaoka Takumi、Tamazawa Nobuyuki、Aung Naing Ye、Utsunomiya Aya、Toubai Tomomi、Ishizawa Kenichi
  • Journal Title: Case Reports in Oncology Volume: 13 Issue: 3 Pages: 1145-1151
  • DOI: 10.1159/000510362
  • Peer Reviewed / Open Access
• [Journal Article] Good Prognosis for Follicular Lymphoma with Estrogen Receptor α-positive Follicular Dendritic Cells (2020)
  • Author(s): Ohe Rintaro、Meng Hong-Xue、Yamada Akane、Aung Naing Ye、Kabasawa Takanobu、Tamura Yuka、Utsunomiya Aya、Tamazawa Nobuyuki、Kawamura Ichiro、Kitaoka Takumi、Suzuki Kazushi、Yanagiya Ryo、Toubai Tomomi、Ishizawa Kenichi、Yamakawa Mitsunori
  • Journal Title: Hematological Oncology Volume: - Issue: 3 Pages: 293-300
  • DOI: 10.1002/hon.2730
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A case of iatrogenic immunodeficiency-associated colonic lymphoma complicating ulcerative colitis (2020)
  • Author(s): Suzuki Kazushi、Ohe Rintaro、Kabasawa Takanobu、Aung Naing Ye、Yano Mitsuhiro、Katsumi Shuichiro、Yanagiya Ryo、Yamamoto Masakazu、Toubai Tomomi、Ishizawa Kenichi、Yamakawa Mitsunori
  • Journal Title: Diagnostic Pathology Volume: 15 Issue: 1 Pages: 34-34
  • DOI: 10.1186/s13000-020-00954-8
  • Peer Reviewed / Open Access
• [Journal Article] Comparative study of HO-1 expressing synovial lining cells between RA and OA (2020)
  • Author(s): Yang Suran、Ohe Rintaro、Aung Naing Ye、Kato Tomoya、Kabasawa Takanobu、Utsunomiya Aya、Takakubo Yuya、Takagi Michiaki、Yamakawa Mitsunori
  • Journal Title: Modern Rheumatology Volume: - Issue: 1 Pages: 1-8
  • DOI: 10.1080/14397595.2019.1704976
  • Peer Reviewed
• [Journal Article] Diagnostic Utility of CD205 in Breast Cancer: Simultaneous Detection of Myoepithelial Cells and Dendritic Cells in Breast Tissue by CD205 (2020)
  • Author(s): Ohe Rintaro, Naing Ye Aung, Tamura Yuka, Kabasawa Takanobu, Utsunomiya Aya, Tamazawa Nobuyuki, Kitaoka Takumi, Meng Hong-Xue, Shibata Kenichi, Yamakawa Mitsunori
  • Journal Title: Histology and Histopathology Volume: 35 Pages: 481-488
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Differential expression of estrogen receptor-α on follicular dendritic cells from patients with grade 1-2 and grade 3 follicular lymphoma (2019)
  • Author(s): Ohe R, Meng HX, Ye Aung N, Yamada A, Kabasawa T, Utsunomiya A, Tamazawa N, Tamura Y, Kitaoka T, Hashimoto T, Shibata K, Toubai T, Kimura W, Ishizawa K, Yamakawa M
  • Journal Title: Hematol Oncol Volume: 37 Issue: 2 Pages: 151-159
  • DOI: 10.1002/hon.2577
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] エストロゲン受容体α陽性の 濾胞樹状細胞の存在は濾胞性リンパ腫の 予後良好因子である (2020)
  • Author(s): 大江倫太郎, 孟宏学, 山田茜, ナイン・イエイ・アウン, 樺澤崇允, 宇都宮文, 玉澤暢之, 北岡匠, 石澤賢一, 山川光徳
  • Organizer: 第109回日本病理学会総会