Development of immune biomarkers by turmoral microbiome in head and neck cancer

• Project/Area Number: 20K18331
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Aichi Cancer Center Research Institute
• Principal Investigator: Sawabe Michi 愛知県がんセンター(研究所), 腫瘍免疫制御TR分野, 研究員 (30790711)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2022: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 頭頸部癌 / 頭頸部がん / 腫瘍内細菌叢 / 葉酸摂取 / ５－FU / 抗腫瘍免疫 / 頭頚部癌 / バイオマーカー

Outline of Research at the Start

大腸がんや膵臓がんでは、口腔内常在菌などの細菌が腫瘍組織の内部に存在し、抗腫瘍免疫を抑制してがんの進展に関与することが明らかになった。本研究では、頭頸部がんの腫瘍内の細菌叢に着目し、腫瘍組織や転移リンパ節内の細菌叢が、抗腫瘍免疫に与える影響を評価する。本研究の目的は、抗腫瘍免疫を抑制する腫瘍内細菌叢の存在を明らかにすることである。

Outline of Final Research Achievements

Fluorouracil (FU) is an antitumor agent that works by inhibiting folic acid-mediated one-carbon metabolism. The chemosensitivity of patients to induction chemotherapy (IC) involving FU in head and neck cancer varies due to differences in prediagnostic folic acid intake. Folic acid is believed to play a role in the development of cancer through folic acid-mediated one-carbon metabolism. To investigate this hypothesis, a cohort study was conducted on 504 patients diagnosed with locally advanced head and neck squamous cell carcinoma (HNSCC) at stage III or IV.
The results of the study revealed a significant variation in the association between prediagnostic folic acid intake and HNSCC survival, particularly in cases where FU-containing IC was administered. This suggests that the status of folic acid during carcinogenesis contributes to the heterogeneity observed in HNSCC, specifically in terms of one-carbon metabolism.

Academic Significance and Societal Importance of the Research Achievements

本研究により頭頸部癌の異質性の原因が、それまでの環境要因であることを示す。頭頸部癌の異質性を多方面より評価することで、治療への応用にも応用が期待できる。

Research Products

• [Journal Article] Clinical impact of weekly paclitaxel plus cetuximab is comparable to the EXTREME regimen for recurrent/metastatic head and neck squamous cell carcinoma (2021)
  • Author(s): Motai Risa、Sawabe Michi、Kadowaki Shigenori、Sasaki Eiichi、Nishikawa Daisuke、Suzuki Hidenori、Beppu Shintaro、Terada Hoshino、Hanai Nobuhiro
  • Journal Title: International Journal of Clinical Oncology Volume: online Issue: 7 Pages: 1188-1195
  • DOI: 10.1007/s10147-021-01907-x
  • Peer Reviewed
• [Journal Article] Real-World, Long-Term Outcomes of Nivolumab Therapy for Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck and Impact of the Magnitude of Best Overall Response: A Retrospective Multicenter Study of 88 Patients. (2020)
  • Author(s): Matsuki T, Okamoto I, Fushimi C, Takahashi H, Okada T, Kondo T, Sato H, Ito T, Tokashiki K, Tsukahara K, Hanyu K, Masubuchi T, Tada Y, Miura K, Omura G, Sawabe M, Kawakita D, Yamashita T
  • Journal Title: Cancers Volume: 12 Issue: 11 Pages: 3427-3427
  • DOI: 10.3390/cancers12113427
  • Peer Reviewed / Open Access
• [Journal Article] Eosinophil prognostic scores for patients with head and neck squamous cell carcinoma treated with nivolumab (2020)
  • Author(s): Nishikawa Daisuke、Suzuki Hidenori、Beppu Shintaro、Terada Hoshino、Sawabe Michi、Kadowaki Shigenori、Sone Michihiko、Hanai Nobuhiro
  • Journal Title: Cancer Science Volume: 112 Issue: 1 Pages: 339-346
  • DOI: 10.1111/cas.14706
  • Peer Reviewed / Open Access