Development of early diagnostic method and order-made immunotherapy for oral cancer by using anti-tumor T cells

• Project/Area Number: 24249091
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Kyushu University
• Principal Investigator: Nakamura Seiji 九州大学, 歯学研究院, 教授 (60189040)
• Co-Investigator(Kenkyū-buntansha): 豊嶋 健史 九州大学, 歯学研究科(研究院), 研究員 (20546569) ; 吉田 裕樹 佐賀大学, 医学部, 教授 (40260715) ; 山田 亮 久留米大学, 付置研究所, 教授 (50158177)
• Project Period (FY): 2012-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥46,800,000 (Direct Cost: ¥36,000,000、Indirect Cost: ¥10,800,000); Fiscal Year 2016: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2015: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2014: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2013: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2012: ¥34,970,000 (Direct Cost: ¥26,900,000、Indirect Cost: ¥8,070,000)
• Keywords: オーダーメイド免疫療法 / 口腔扁平上皮癌 / RCAS1 / PD-L1 / 腫瘍会合性マクロファージ / 腫瘍免疫 / 免疫チェックポイント分子 / 腫瘍随伴性マクロファージ / 癌ペプチド / オーダーメイドワクチン / 口腔癌 / T細胞 / アポトーシス

Outline of Final Research Achievements

Receptor-binding cancer antigen expressed on SiSo cell (RCAS1) is derived from uterine adenocarcinoma and can induce apoptosis in lymphocytes. In this study, we investigated expression patterns of RCAS1 and the effect on apoptosis in oral squamous cell carcinoma (OSCC). RCAS1 mRNA and proteins were expressed in all of OSCC cell lines. Membranous pattern were expressed in all cell lines, while soluble pattern was detected in all supernatants. RCAS1 mRNA, membranous and soluble RCAS1 were significantly seen in SQUU-B more than the other 3 cell lines. K562 apoptosis was induced in co-culture with each of all cell lines, particularly with SQUU-B. Apoptosis was markedly reduced in co-culture with RCAS1 knockdown cells, but was induced in co-culture without cell contract of SQUU-B. Our study suggests that RCAS1 has an apoptotic function via membranous/soluble expression pattern in OSCC cells. RCAS1 may thus affect tumor escape from immune surveillance in OSCC by inducing apoptosis.

Research Products

• [Journal Article] CD163+CD204+ tumor-associated macrophages contribute to T cell regulation via interleukin-10 and PD-L1 production in oral squamous cell carcinoma. (2017)
  • Author(s): Kubota K, Moriyama M, Furukawa S, Haque R ASM, Maruse Y, Jinno T, Tanaka A, Ohta M, Ishiguro N, Yamauchi M, Sakamoto M, Maehara T, Hayashida JN, Kawano S, Kiyoshima T, and Nakamura S
  • Journal Title: Sci Rep Volume: 印刷中
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] GLI-mediated Keratin 17 expression promotes tumor cell growth through the anti-apoptotic function in oral squamous cell carcinomas. (2017)
  • Author(s): Mikami Y, Fujii S, Nagata K, Wada H, Hasegawa K, Abe M, Yoshimoto RU, Kawano S, Nakamura S, Kiyoshima T
  • Journal Title: Journal of Cancer Research and Clinical Oncology Volume: 印刷中 Pages: 1381-1393
  • DOI: 10.1007/s00432-017-2398-2
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Critical roles of Wnt5a-Ror2 signaling in aggressiveness of tongue squamous cell carcinoma and production of matrix metalloprotease-2 via ΔNp63β-mediated epithelial-mesenchymal transition. (2017)
  • Author(s): Sakamoto T, Kawano S, Matsubara R, Goto Y, Jinno T, Maruse Y, Kaneko N, Hashiguchi Y, Hattori T, Tanaka S, Kitamura R, Kiyoshima T, Nakamura S
  • Journal Title: Oral Oncol Volume: 印刷中
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A case of marginal zone B cell lymphoma mimicking IgG4-related dacryoadenitis and sialoadenitis (2015)
  • Author(s): Ohta M, Moriyama M, Goto Y, Kawano S, Tanaka A, Maehara T, Furukawa S, Hayashida JN, Kiyoshima T, Shimizu M, Arinobu Y, Nakamura S.
  • Journal Title: World Journal of Surgical Oncology Volume: 13 Pages: 67-67
  • DOI: 10.1186/s12957-015-0459-z
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Increased expression of interleukin-6 predicts poor response to chemoradiotherapy and unfavorable prognosis in oral squamous cell carcinoma (2015)
  • Author(s): Jinno T, Kawano S, Maruse Y, Matsubara R, Goto Y, Sakamoto T, Hashiguchi Y, Kaneko N, Tanaka H, Kitamura R, Toyoshima T, Jinno A, Moriyama M, Oobu K, Kiyoshima T, Nakamura S
  • Journal Title: Oncol Rep Volume: 33 Pages: 2161-2168
  • DOI: 10.3892/or.2015.3838
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A case of mantle cell lymphoma presenting as IgG4-related dacryoadenitis and sialoadenitis, so-called Mikulicz's disease. (2015)
  • Author(s): Hayashi Y, Moriyama M, M Takashi, Goto Y, Kawano S, Ohta M, Tanaka A, Furukawa S, Hayashida JN, Kiyoshima T, Shimizu M, Chikui T, Nakamura S.
  • Journal Title: World J Surg Oncol Volume: 13 Pages: 225-225
  • DOI: 10.1186/s12957-015-0644-0
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Possible involvement of ΔNp63 downregulation in the invasion and metastasis of oral squamous cell carcinoma via induction of a mesenchymal phenotype. (2014)
  • Author(s): Yuichi Goto, Shintaro Kawano, Ryota Matsubara, Takahiro Kiyosue, Mitsuhiro Hirano, Teppei Jinno, Yasuyuki Maruse, Toyoshima Takeshi, Ryoji Kitamura, Hideaki Tanaka, Kazunari Oobu, Seiji Nakamura
  • Journal Title: Clin Exp Metastasis Volume: 214 Pages: 289-306
  • DOI: 10.1007/s10585-013-9628-z
  • Peer Reviewed / Open Access
• [Journal Article] Apoptotic function of tumor-associated antigen RCAS1 in oral squamous cell carcinoma (2014)
  • Author(s): Hideaki Tanaka, Takeshi Toyoshima, Kenzo Sonoda, Ryoji Kitamura, Masaaki Sasaguri, Shintaro Kawano, Ryota Matsubara, Yuichi Goto, Seiji Nakamura
  • Journal Title: Journal of Translational Medicine Volume: in press
  • Peer Reviewed
• [Journal Article] In vitro induction of specific CD8+ T lymphocytes by tumor-associated antigenic peptides in patients with oral squamous cell carcinoma (2012)
  • Author(s): Toyoshima, T., Kumamaru, W., Hayashida, J.-N., Moriyama, M., Kitamura, R., Tanaka, H., Yamada, A., Itoh, K., and Nakamura, S.
  • Journal Title: Cancer Lett. Volume: 322 Pages: 86-91
  • DOI: 10.1016/j.canlet.2012.02.016
  • Peer Reviewed
• [Presentation] 口腔扁平上皮癌における免疫回避機構と腫瘍随伴性マクロファージとの関連 (2016)
  • Author(s): 久保田 恵吾、森山 雅文、古川 祥子、Haque ASM Rafiul、丸瀬 靖之、川野 真太郎、林田 淳之介、太田 美穂、清島 保、中村 誠司
  • Organizer: 第44回日本臨床免疫学会総会
  • Place of Presentation: 東京
  • Year and Date: 2016-09-08
• [Presentation] 口腔扁平上皮癌由来細胞株における腫瘍関連抗原RCAS1(receptor-binding caner antigen expressed on SiSo cells)の発現と機能についての検討 (2013)
  • Author(s): 田中 秀明
  • Organizer: 第 31 回日本口腔腫瘍学会
  • Place of Presentation: 東京
• [Presentation] 口腔扁平上皮癌由来細胞株における腫瘍関連抗原RCAS1の発現、分泌と機能についての検討
  • Author(s): 田中秀明，豊嶋健史，園田顕三，北村亮二，川野真太郎，平野充広，神野哲平，丸瀬靖之，笹栗正明，大部一成，中村誠司
  • Organizer: 第67回日本口腔科学会学術集会
  • Place of Presentation: 栃木
• [Presentation] 口腔扁平上皮癌由来細胞株における腫瘍関連抗原RCAS1の発現と機能についての検討
  • Author(s): 田中秀明，豊嶋健史，園田顕三，北村亮二，川野真太郎，平野充広，神野哲平，丸瀬靖之，笹栗正明，大部一成，中村誠司
  • Organizer: 第58回日本口腔外科学会総会•学術大会
  • Place of Presentation: 福岡