Immunogenomic profile associated with response to neoadjuvant chemoradiotherapy in patients with rectal cancer

• Project/Area Number: 18K08664
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: AKIYOSHI Takashi 公益財団法人がん研究会, 有明病院 大腸外科, 副部長 (50625598)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 直腸癌 / 術前放射線化学療法 / 免疫ゲノム解析 / 化学放射線療法 / 微小免疫環境 / TCRレパトア / 放射線化学療法 / 免疫環境

Outline of Final Research Achievements

The significance of T-cell complexity in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy (CRT) remains unknown. High-throughput T-cell receptor (TCR) β sequencing was applied to quantify the TCR repertoire of pre-treatment biopsies from 67 patients with advanced rectal cancer receiving preoperative CRT. Diversity index was used to represent the complexity of the TCR repertoire in a tumor. Changes in TCR repertoire before and after CRT were also analyzed in 23 patients. Diversity indices were significantly higher for good responders than for non-responders. Larger changes in TCR repertoires before and after CRT were correlated with better recurrence-free survival. The complexity and dynamic change in the TCR repertoire might serve as a useful indicator of response to CRT in patients with rectal cancer.

Academic Significance and Societal Importance of the Research Achievements

腫瘍浸潤CD8陽性T細胞の密度が直腸癌に対する術前化学放射線療法(CRT)の治療効果と相関することはこれまで報告されていたが、本研究でははじめて腫瘍浸潤CD8陽性T細胞の密度だけでなくT細胞レパトアの多様性がCRTの治療効果の予測に有用であることを示した。

Research Products

• [Journal Article] Serial circulating tumour DNA analysis for locally advanced rectal cancer treated with preoperative therapy: prediction of pathological response and postoperative recurrence (2020)
  • Author(s): Murahashi Satoshi、Akiyoshi Takashi、Sano Takeshi、Fukunaga Yosuke、Noda Tetsuo、Ueno Masashi、Zembutsu Hitoshi
  • Journal Title: British Journal of Cancer Volume: - Issue: 5 Pages: 803-810
  • DOI: 10.1038/s41416-020-0941-4
  • Peer Reviewed
• [Journal Article] Radiomics Approach Outperforms Diameter Criteria for Predicting Pathological Lateral Lymph Node Metastasis After Neoadjuvant (Chemo)Radiotherapy in Advanced Low Rectal Cancer (2020)
  • Author(s): Nakanishi Ryota、Akiyoshi Takashi、Toda Shigeo、Murakami Yu、Taguchi Senzo、Oba Koji、Hanaoka Yutaka、Nagasaki Toshiya、Yamaguchi Tomohiro、Konishi Tsuyoshi、Matoba Shuichiro、Ueno Masashi、Fukunaga Yosuke、Kuroyanagi Hiroya
  • Journal Title: Annals of Surgical Oncology Volume: 27 Issue: 11 Pages: 4273-4283
  • DOI: 10.1245/s10434-020-08974-w
  • Peer Reviewed
• [Journal Article] T-cell complexity and density are associated with sensitivity to neoadjuvant chemoradiotherapy in patients with rectal cancer (2020)
  • Author(s): Akiyoshi T, Gotoh O, Tanaka N, Kiyotani K, Yamamoto N, Ueno M, Fukunaga Y, Mori S.
  • Journal Title: Cancer Immunology, Immunotherapy Volume: 70 Issue: 2 Pages: 509-518
  • DOI: 10.1007/s00262-020-02705-6
  • Peer Reviewed / Open Access
• [Journal Article] The advantage of one‐step nucleic acid amplification for the diagnosis of lymph node metastasis in colorectal cancer patients (2020)
  • Author(s): Hiyoshi Yukiharu、Akiyoshi Takashi、Fukunaga Yosuke
  • Journal Title: Annals of Gastroenterological Surgery Volume: 5 Issue: 1 Pages: 60-66
  • DOI: 10.1002/ags3.12392
  • Peer Reviewed
• [Journal Article] Immunogenomic profiles associated with response to neoadjuvant chemoradiotherapy in patients with rectal cancer (2019)
  • Author(s): Akiyoshi T, Tanaka N, Kiyotani K, Gotoh O, Yamamoto N, Oba K, Fukunaga Y, Ueno M, Mori S
  • Journal Title: Br J Surg Volume: 106 Issue: 10 Pages: 1381-1392
  • DOI: 10.1002/bjs.11179
  • Peer Reviewed
• [Journal Article] Prognostic value of metastatic lymph node regression grade after neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer (2019)
  • Author(s): Tominaga T, Akiyoshi T, Yamamoto N, Oba K, Nagasaki T, Yamaguchi T, Konishi T, Fukunaga Y, Ueno M
  • Journal Title: Surgery Volume: 166 Issue: 6 Pages: 1061-1067
  • DOI: 10.1016/j.surg.2019.06.009
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Comprehensive Comparative Analysis of Prognostic Value of Systemic Inflammatory Biomarkers for Patients with Stage II/III Colon Cancer (2019)
  • Author(s): Suzuki S, Akiyoshi T, Oba K, Otsuka F, Tominaga T, Nagasaki T, Fukunaga Y, Ueno M
  • Journal Title: Ann Surg Oncol Volume: 27 Issue: 3 Pages: 844-852
  • DOI: 10.1245/s10434-019-07904-9
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Prognostic impact of residual lateral lymph node metastasis after neoadjuvant (chemo)radiotherapy in patients with advanced low rectal cancer (2019)
  • Author(s): Akiyoshi T, Toda S, Tominaga T, Oba K, Tomizawa K, Hanaoka Y, Nagasaki T, Konishi T, Matoba S, Fukunaga Y, Ueno M, Kuroyanagi H
  • Journal Title: BJS Open Volume: 3 Issue: 6 Pages: 822-829
  • DOI: 10.1002/bjs5.50194
  • Peer Reviewed / Open Access
• [Journal Article] Clinical significance of soluble programmed cell death-1 and soluble programmed cell death-ligand 1 in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy (2019)
  • Author(s): Tominaga T, Akiyoshi T, Yamamoto N, Taguchi S, Mori S, Nagasaki T, Fukunaga Y, Ueno M
  • Journal Title: PLoS One Volume: 14 Issue: 2 Pages: e0212978-e0212978
  • DOI: 10.1371/journal.pone.0212978
  • Peer Reviewed / Open Access
• [Journal Article] Pattern of programmed cell death-ligand 1 expression and CD8-positive T-cell infiltration before and after chemoradiotherapy in rectal cancer (2018)
  • Author(s): Ogura Atsushi、Akiyoshi Takashi、Yamamoto Noriko、Kawachi Hiroshi、Ishikawa Yuichi、Mori Seiichi、Oba Koji、Nagino Masato、Fukunaga Yosuke、Ueno Masashi
  • Journal Title: European Journal of Cancer Volume: 91 Pages: 11-20
  • DOI: 10.1016/j.ejca.2017.12.005
  • Peer Reviewed / Open Access
• [Presentation] 当院における進行直腸癌に対するwatch and waitの治療成績 (2020)
  • Author(s): 秋吉 高志, 村橋 賢, 向井 俊貴, 長嵜 寿也, 山口 智弘, 小西 毅, 長山 聡, 上野 雅資, 福長 洋介
  • Organizer: 第75回日本消化器外科学会総会
• [Presentation] Immunogenomic profiles associated with response to neoadjuvant chemoradiotherapy in patients with advanced low rectal cancer (2020)
  • Author(s): 秋吉 高志, 森 誠一, 清谷 一馬, 向井 俊貴, 長嵜 寿也, 山口 智弘, 小西 毅, 長山 聡, 福長 洋介, 上野 雅資
  • Organizer: 第120回日本外科学会定期学術集会
• [Presentation] 術前治療を施行した進行直腸癌症例を用いたcirculating tumor DNAと術後再発の関連解析 (2020)
  • Author(s): 村橋 賢, 秋吉 高志, 向井 俊貴, 山口 智弘, 長嵜 寿矢, 小西 毅, 長山 聡, 上野 雅資, 福長 洋介
  • Organizer: 第120回日本外科学会総会定期学術集会