Clinical Significance of Regulatory T Cells in Regional Lymph Node Lymphocytes of Non-Small-Cell Lung Cancer and overcoming immune-escape mechanism

• Project/Area Number: 23592079
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: HANAGIRI Takeshi 産業医科大学, 医学部, 非常勤医師 (30299614)
• Co-Investigator(Kenkyū-buntansha): 竹之山 光広 国立病院機構九州がんセンター, 医学部, 呼吸器腫瘍科医長 (10309966) ; 浦本 秀隆 産業医科大学, 医学部, 准教授 (90389445) ; 重松 義紀 産業医科大学, 医学部, 助教 (10546469)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 肺癌 / 制御性T細胞 / 腫瘍免疫 / 免疫逃避 / 細胞障害性T細胞 / 免疫逃避機構 / 制御性Ｔ細胞 / TGF-β / Foxp3 / 所属リンパ節 / 制御性Tリンパ球 / フローサイトメトリ / リアルタイムPCR

Research Abstract

Regulatory T cells (Tregs) are potent immunosuppressive cells that play a crucial role in tumor immune escape. The purpose of the present study was to evaluate the prognostic significance of CD4+ CD25+ Foxp3+ Tregs in the regional lymph node lymphocytes (RLNL) in patients who underwent surgical resection of non-small cell lung cancer (NSCLC). The proportions of Tregs in the RLNL were determined by flow cytometry and quantitative RT–PCR. The 5-year survival rate was significantly better in patients with the lower proportion of Tregs than that in the higher patients. The higher proportion of Tregs in the RLNL was a significant unfavorable prognostic factor in NSCLC. The information about the proportion of Tregs in the RLNL is considered to be important to overcome the tumor immune escape for development of the effective adjuvant immunotherapy

Research Products

• [Journal Article] Clinical significance of expression of cancer/testis antigen and down-regulation of HLA class-I in patients with stage I non-small cell lung cancer (2013)
  • Author(s): Hanagiri T, Shigematsu Y, Shinohara S, Takenaka M, Oka S, Chikaishi Y, Nagata Y, Baba T, Uramoto H, So T, Yamada S
  • Journal Title: Anticancer Res Volume: 33 Pages: 2123-8
• [Journal Article] Clinical significance of the frequency of regulatory T cells in regional lymph node lymphocytes as a prognostic factor for non-small-cell lung cancer (2013)
  • Author(s): Hanagiri T, Shigematsu Y, Shinohara S, Takenaka M, Oka S, Chikaishi Y, Nagata Y, Iwata T, Uramoto H, So T, Tanaka F
  • Journal Title: Lung Cancer Volume: 81 Pages: 475-9
• [Journal Article] Prognostic implications of human leukocyte antigen class I expression in patients who underwent surgical resection for non-small-cell lung cancer (2013)
  • Author(s): Hanagiri T, Shigematsu Y, Kuroda K, Baba T, Shiota H, Ichiki Y, Nagata Y, Yasuda M, Uramoto H, So T, Takenoyama M, Tanaka F
  • Journal Title: J Surg Res Volume: 181
• [Journal Article] Clinical significance of expression of cancer/testis antigen and down-regulation of HLA class-I in patients with stage I non-small cell lung cancer. (2013)
  • Author(s): Hanagiri T
  • Journal Title: Anticancer Res Volume: 33 Issue: 1 Pages: 2123-8
  • DOI: 10.1016/j.lungcan.2009.05.010
  • Peer Reviewed
• [Journal Article] Immunosuppressive effect of regulatory T lymphocytes in lung cancer, with special reference to their effects on the induction of autologous tumor-specific cytotoxic T lymphocytes (2012)
  • Author(s): Shigematsu Y, Hanagiri T, Shiota H, Kuroda K, Baba T, Ichiki Y, Yasuda M, Uramoto H, Takenoyama M, Yasumoto K, Tanaka F
  • Journal Title: Oncol Lett Volume: 4 Pages: 625-630
• [Journal Article] Immunosuppressive effect of regulatory T lymphocytes in lung cancer, with special reference to their effects on the induction of autologous tumor-specific cytotoxic T lymphocytes. (2012)
  • Author(s): Shigematsu Y, Hanagiri T (2番目/12人中）
  • Journal Title: Oncol Lett Volume: 4 Pages: 625-630
  • Peer Reviewed
• [Journal Article] Prognostic implications of human leukocyte antigen class I expression in patients who underwent surgical resection for non-small-cell lung cancer. (2012)
  • Author(s): Hanagiri T
  • Journal Title: J Surg Res Volume: 181 Pages: 57-63
  • Peer Reviewed
• [Journal Article] Preoperative CYFRA 21-1 and CEA as prognostic factors in patientswith stage I non-small cell lung cancer (2011)
  • Author(s): Hanagiri T, Sugaya M, Takenaka M, Oka S, Baba T, Shigematsu Y, Nagata Y, Shimokawa H, Uramoto H, Takenoyama M, Yasumoto K, Tanaka F
  • Journal Title: Lung Cancer Volume: 74 Issue: 1 Pages: 112-117
  • DOI: 10.1016/j.lungcan.2011.02.001
  • Peer Reviewed
• [Journal Article] Clinical significance in the number of involved lymph nodes inpatients that underwent surgery for pathological stage III-N2 non-small cell lung cancer (2011)
  • Author(s): Hanagiri T
  • Journal Title: J Cardiothorac Surg Volume: 25 Issue: 1 Pages: 144-144
  • DOI: 10.1186/1749-8090-6-144
  • Peer Reviewed
• [Journal Article] Prognostic Significance of Lymphovascular Invasion for Patients withStage I Non-Small Cell Lung Cancer (2011)
  • Author(s): Hanagiri T, Takenaka M, Oka S, Shigematsu Y, Nagata Y, Shimokawa H, Uramoto H, Yamada S, Tanaka F
  • Journal Title: Eur Surg Res Volume: 47 Issue: 4 Pages: 211-217
  • DOI: 10.1159/000333367
  • Peer Reviewed
• [Presentation] 非小細胞肺癌におけるFoxp3およびIDO発現の臨床病理学的意義産業 (2013)
  • Author(s): 花桐武志、重松義紀、平井文子、竹中賢、岡壮一、近石泰弘、岩浪崇嗣、下川秀彦、永田好香、浦本秀隆、宗知子、田中文啓
  • Organizer: 日本肺癌学会
  • Place of Presentation: 医科大学第2外科
• [Presentation] 肺癌所属リンパ節における制御性T細胞および微小リンパ節転移の意義 (2013)
  • Author(s): 花桐武志、重松義紀、竹中賢、岡壮一、近石泰弘、下川秀彦、中川誠、永田好香、岩田輝男、浦本秀隆、宗知子、田中文啓
  • Organizer: 日本呼吸器外科学会
  • Place of Presentation: 産業医科大学第2外科
• [Presentation] 肺癌所属リンパ節における制御性T細胞および微小リンパ節転移の意義 (2013)
  • Author(s): 花桐武志
  • Organizer: 第30回日本呼吸器外科学会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] 非小細胞肺癌におけるFoxp3およびIDO発現の臨床病理学的意義 (2013)
  • Author(s): 花桐武志
  • Organizer: 第５４回日本肺癌学会
  • Place of Presentation: ホテルニューオータニ東京
• [Presentation] 肺癌所属リンパ節における制御性T細胞の臨床病理学的意義 (2012)
  • Author(s): 花桐武志,重松義紀,竹中賢,岡壮一,近石泰弘,下川秀彦,中川誠,永田好香,岩田輝男,浦本秀隆,宗知子,田中文啓
  • Organizer: 日本肺癌学会
• [Presentation] 肺癌所属リンパ節における制御性T細胞および微小リンパ節転移の解析 (2012)
  • Author(s): 花桐武志,重松義紀,竹中賢,岡壮一,近石泰弘,下川秀彦,中川誠,永田好香,浦本秀隆,宗知子,田中文啓
  • Organizer: 日本癌治療学会
• [Presentation] 非小細胞肺癌における腫瘍抗原およびHLA class Iの発現;癌特異的免疫療法への基盤的研究 (2012)
  • Author(s): 花桐武志,黒田耕志、重松義紀,永田好香,馬場哲郎,浦本秀隆,宗知子,竹之山光広,田中文啓
  • Organizer: 日本呼吸器外科学会
• [Presentation] 非小細胞肺癌における癌精巣抗原発現とワクチン療法への応用 (2012)
  • Author(s): 重松義紀,竹中賢,岡壮一,近石泰弘,馬場哲郎,下川秀彦,中川誠,浦本秀隆,宗知子,花桐武志,田中文啓
  • Organizer: 日本外科学会
• [Presentation] 肺癌所属リンパ節における制御性T細胞および微小リンパ節転移の解析 (2012)
  • Author(s): 花桐 武志
  • Organizer: 第50回日本癌治療学会
  • Place of Presentation: 岡山コンベンションセンター（岡山）
• [Presentation] 肺癌所属リンパ節における制御性T細胞の臨床病理学的意義 (2012)
  • Author(s): 花桐 武志
  • Organizer: 第53回日本肺癌学会
  • Place of Presentation: 幕張メッセ（千葉）
• [Presentation] 非小細胞肺癌における癌精巣抗原発現とワクチン療法への応用 (2012)
  • Author(s): 重松 義紀, 竹中 賢, 岡 壮一, 近石 泰弘, 馬場 哲郎, 下川 秀彦, 中川 誠, 浦本 秀隆, 宗 知子, 花桐 武志, 田中 文啓（10番目/11人中）
  • Organizer: 第112回日本外科学会
  • Place of Presentation: 幕張メッセ（千葉）
• [Presentation] 非小細胞肺癌における腫瘍抗原およびHLA class Iの発現；癌特異的免疫療法への基盤的研究 (2012)
  • Author(s): 花桐 武志
  • Organizer: 第29回日本呼吸器外科学会
  • Place of Presentation: 秋田キャッスルホテル（秋田）
• [Presentation] pN2-III期非小細胞肺癌に対する外科切除例の検討 (2011)
  • Author(s): (1)竹中賢，中川誠，篠原伸二，桒田泰治，岡壮一，近石泰弘，重松義紀，永田好香，下川秀彦，浦本秀隆，宗知子，花桐武志，田中文啓
  • Organizer: 第52回日本肺癌学会総会
  • Place of Presentation: 大阪国際会議場（大阪）
• [Presentation] 肺癌患者における制御性Ｔ細胞の発現と役割 (2011)
  • Author(s): (2)重松義紀，黒田耕志，馬場哲郎，竹中賢，近石泰弘，岡壮一，中川誠，下川秀彦，浦本秀隆，宗知子，花桐武志，田中文啓
  • Organizer: 免疫疾患学会連合2011
  • Place of Presentation: 京王プラザホテル（東京）
• [Presentation] 病理病期I期原発性肺癌切除例における予後因子としての術前腫瘍マーカー (2011)
  • Author(s): (3)花桐武志，岡壮一，馬場哲郎，永田好香，重松義紀，下川秀彦，浦本秀隆，竹之山光広，田中文啓
  • Organizer: 第28回日本呼吸器外科学会総会
  • Place of Presentation: 別府国際コンベンションセンター（別府）