The role of regulatory T cell and related chemokines in urothelial carcinoma of the bladder

• Project/Area Number: 16K20159
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Nara Medical University
• Principal Investigator: Miyake Makito 奈良県立医科大学, 医学部, 助教 (80601400)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 膀胱癌 / 免疫細胞 / 制御性 T 細胞 / 腫瘍関連マクロファージ / BCG 膀胱注入療法 / 骨髄由来免疫抑制細胞 / BCG膀胱注入療法 / 癌微小環境 / 尿路上皮癌 / 制御性T細胞 / 癌関連マクロファージ / サイトカイン / 癌 / ケモカイン / 腫瘍免疫 / 免疫治療

Outline of Final Research Achievements

The aim of this project is to evaluate the association between topical immunostatus/systemic inflammation and the risk of BCG refractory non-muscle invasive disease and metastatic muscle invasive disease. The immunohistochemical staining analysis of tumor tissue specimes with FOXP3 (Treg maker) and CD204 (TAM marker) antibodies revealed that high counts of Treg and TAM were associated with shorter recurrence-free survival and disease-free survival. The time-couse analysis of urine obtained from patients treated with intravesical BCG demonstarted that the expression of T cell makers including FOXP3 was increased with time. On the otherhand, B cell-related antigens showed much less chage compared to T cell-related antigens. We will accumulate the patients number.

Research Products

• [Journal Article] Clinical utility of bioelectrical impedance analysis in patients with locoregional muscle invasive or metastatic urothelial carcinoma: a subanalysis of changes in body composition during neoadjuvant systemic chemotherapy (2018)
  • Author(s): Miyake M, Owari T, Iwamoto T, Morizawa Y, Hori S, Marugami N, Shimada K, Iida K, Ohnishi K, Gotoh D, Tatsumi Y, Nakai Y, Inoue T, Anai S, Torimoto K, Aoki K, Yoneda T, Tanaka N, Fujimoto K
  • Journal Title: Support Care Cancer Volume: 26 Issue: 4 Pages: 1077-1086
  • DOI: 10.1007/s00520-017-3924-0
  • Peer Reviewed
• [Journal Article] Gamma-Klotho exhibits multiple roles in tumor growth of human bladder cancer. (2018)
  • Author(s): Hori S, Miyake M, Tatsumi Y, Morizawa Y, Nakai Y, Onishi S, Onishi K, Iida K, Gotoh D, Tanaka N, Fujimoto K.
  • Journal Title: Oncotarget Volume: 9 Issue: 28 Pages: 19508-19524
  • DOI: 10.18632/oncotarget.24628
  • Peer Reviewed / Open Access
• [Journal Article] Clinical impact of postoperative loss in psoas major muscle and nutrition index after radical cystectomy for patients with urothelial carcinoma of the bladder (2017)
  • Author(s): Miyake M, Morizawa Y, Hori S, Marugami N, Shimada K, Gotoh D, Tatsumi Y, Nakai Y, Inoue T, Anai S, Torimoto K, Aoki K, Tanaka N, Fujimoto K
  • Journal Title: BMC Cancer Volume: 17 Issue: 1 Pages: 237-237
  • DOI: 10.1186/s12885-017-3231-7
  • Peer Reviewed / Open Access
• [Journal Article] Topical and systemic immunoreaction triggered by intravesical chemotherapy in an N-butyl-N-(4-hydroxybutyl) nitorosamine induced bladder cancer mouse model. (2017)
  • Author(s): Hori S, Miyake M, Tatsumi Y, Onishi S, Morizawa Y, Nakai Y, Tanaka N, Fujimoto K.
  • Journal Title: PLoS One Volume: 12 Issue: 4 Pages: e0175494-e0175494
  • DOI: 10.1371/journal.pone.0175494
  • Peer Reviewed / Open Access
• [Journal Article] Collagen type IV alpha 1 (COL4A1) and collagen type XIII alpha 1 (COL13A1) produced in cancer cells promote tumor budding at the invasion front in human urothelial carcinoma of the bladder. (2017)
  • Author(s): Miyake M, Hori S, Morizawa Y, Tatsumi Y, Toritsuka M, Ohnishi S, Shimada K, Furuya H, Khadka VS, Deng Y, Ohnishi K, Iida K, Gotoh D, Nakai Y, Inoue T, Anai S, Torimoto K, Aoki K, Tanaka N, Konishi N, Fujimoto K.
  • Journal Title: Oncotarget Volume: 8 Issue: 22 Pages: 36099-36114
  • DOI: 10.18632/oncotarget.16432
  • Peer Reviewed / Open Access
• [Journal Article] Integrative Assessment of Pretreatment Inflammation-, Nutrition-, and Muscle-Based Prognostic Markers in Patients with Muscle-Invasive Bladder Cancer Undergoing Radical Cystectomy (2017)
  • Author(s): Miyake M, Morizawa Y, Hori S, Marugami N, Iida K, Ohnishi K, Gotoh D, Tatsumi Y, Nakai Y, Inoue T, Anai S, Torimoto K, Aoki K, Tanaka N, Shimada K, Konishi N, Fujimoto K
  • Journal Title: Oncology Volume: 93 Issue: 4 Pages: 259-269
  • DOI: 10.1159/000477405
  • Peer Reviewed
• [Journal Article] Diagnostic and prognostic role of urinary collagens in primary human bladder cancer. (2017)
  • Author(s): Miyake M, Morizawa Y, Hori S, Tatsumi Y, Onishi S, Owari T, Iida K, Onishi K, Gotoh D, Nakai Y, Anai S, Chihara Y, Torimoto K, Aoki K, Tanaka N, Shimada K, Konishi N, Fujimoto K.
  • Journal Title: Cancer Sci. Volume: 108 Issue: 11 Pages: 2221-2228
  • DOI: 10.1111/cas.13384
  • Peer Reviewed / Open Access
• [Journal Article] Regulatory T Cells and Tumor-Associated Macrophages in the Tumor Microenvironment in Non-Muscle Invasive Bladder Cancer Treated with Intravesical Bacille Calmette-Guérin: A Long-Term Follow-Up Study of a Japanese Cohort. (2017)
  • Author(s): Miyake M, Tatsumi Y, Gotoh D, Ohnishi S, Owari T, Iida K, Ohnishi K, Hori S, Morizawa Y, Itami Y, Nakai Y, Inoue T, Anai S, Torimoto K, Aoki K, Shimada K, Konishi N, Tanaka N, Fujimoto K.
  • Journal Title: Int J Mol Sci. Volume: 18 Issue: 10 Pages: 2186-2186
  • DOI: 10.3390/ijms18102186
  • Peer Reviewed / Open Access
• [Journal Article] 同所性膀胱癌モデルマウスを用いた BCGおよび抗癌剤膀胱注入療法による誘導免疫の解析 (2017)
  • Author(s): 三宅牧人 堀 俊太 辰巳佳弘 森澤洋介 大西小百合 中井 靖 田中宣道 藤本清秀
  • Journal Title: 泌尿器外科 Volume: 30 Pages: 439-441
• [Presentation] 膀胱癌の浸潤様式 INF c (Tumor budding) 形成に関わる分子機構の解明と新規治療標的としての可能性 (2018)
  • Author(s): 三宅牧人 ほか
  • Organizer: 2018 年 日本泌尿器科分子・細胞研究会
• [Presentation] Altered deposition of collagens promote tumor budding at the tumor invasion front in urothelial carcinoma of the bladder (2018)
  • Author(s): Makito Miyake et al
  • Organizer: 第 33 回 欧州泌尿器科学会
  • Int'l Joint Research
• [Presentation] Intravesical instillation of chemotherapeutic agents enhances immunomodulation of tumor microenvironment status in conventional BCG therapy (2018)
  • Author(s): Shunta Hori, Makito Miyake et al
  • Organizer: 第 33 回 欧州泌尿器科学会
  • Int'l Joint Research
• [Presentation] 筋層浸潤性膀胱癌における癌局所免疫環境と炎症マーカーの関連 (2017)
  • Author(s): 森澤洋介、三宅牧人
  • Organizer: 第13回 奈良尿路上皮癌研究会
  • Place of Presentation: 大阪
  • Year and Date: 2017-03-18
• [Presentation] 筋層浸潤性膀胱癌における末梢血好中球リンパ球比上昇に関連する原発巣微小環境中の免疫細胞と血中サイトカインの同定 (2017)
  • Author(s): 森澤洋介、三宅牧人
  • Organizer: 第26回 泌尿器科分子・細胞研究会
  • Place of Presentation: 大分
  • Year and Date: 2017-03-10
• [Presentation] Postoperative psoas muscle loss and nutritional deterioration after radical cystectomy for patients with invasive bladder cancer (2017)
  • Author(s): Makito Miyake et al
  • Organizer: 第 32 回 欧州泌尿器科学会
  • Int'l Joint Research
• [Presentation] 局所進行性筋層浸潤膀胱癌の生存予後改善と QOL 維持のための治療戦略 (2017)
  • Author(s): 三宅牧人 藤本清秀
  • Organizer: 2017 年 日本泌尿器科学会総会
  • Invited
• [Presentation] 術後経時変化解析からみた膀胱全摘後の腹部筋量低下および栄養指標悪化が予後に及ぼす影響 (2017)
  • Author(s): 三宅牧人 ほか
  • Organizer: 2017 年 日本泌尿器科学会総会
• [Presentation] The diagnostic and prognostic protential of urine COL4A1 and COL13A1 in bladder cancer (2017)
  • Author(s): Makito Miyake et al
  • Organizer: 2017 年 日本癌学会
• [Presentation] 膀胱全摘術前の予後因子の評価と介入について (2017)
  • Author(s): 三宅牧人 藤本清秀
  • Organizer: 2017 年 日本泌尿器科中部総会
  • Invited