Clinical impact of viable circulating tumor cells (v-CTC) detection and PD-L1 expression on v-CTC in the patients with resectable pancreatic cancer

2018 Fiscal Year Annual Research Report

• Project/Area Number: 16K10618
• Research Institution: Osaka University
• Principal Investigator: 種村 匡弘 大阪大学, 医学系研究科, 招へい教員 (30379250)
• Co-Investigator(Kenkyū-buntansha): 三善 英知 大阪大学, 医学系研究科, 教授 (20322183) ; 江口 英利 大阪大学, 医学系研究科, 准教授 (90542118)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 膵癌 / 微小循環癌細胞 / 腹腔内遊離癌細胞 / テロメスキャン / バイオマーカー / 糖鎖 / 糖鎖医薬

Outline of Annual Research Achievements

【背景・目的】末梢血liquid biopsyとして遊離癌細胞(CTC)がある。切除可能膵癌患者(PK)末梢血中の循環癌細胞をTelomeScan F35を応用しviabilityを加味したv-CTC検出に成功した。本研究ではPK患者でのv-CTCの臨床的意義、v-CTC上のPD-L1発現を解析した。【対象】PK 39例を解析した。Surgery first群(S群)、NACRT(N群)で解析した。【結果】[S群]男/女＝12/12、計24例、全例根治切除できた。術前/後を通してv-CTC陰性症例は6例で、5例が無再発生存した。術前/後のいずれかまたは術前/後両測定点でv-CTC陽性例は18例で、13例は根治切除に関わらず早期再発した。術前v-CTC 陽性で術後v-CTC 陰性化またはv-CTCが減少した症例10例でも9例が再発した。[N群]男/女＝4/11、計15例、全例根治切除できた。5例で3点を通してv-CTC陰性で全例無再発生存した。NACRT前よりv-CTC 陽性例6例では、5例がNACRT後にv-CTC数が有意に増加し、内3例で早期肝転移再発しv-CTC 血管内播種誘発が示唆された。[PD-L1発現] S群:18例(内3例CTC陰性)、N群:3例(内1例CTC陰性)で解析した。S群CTCの術前/後での発現率は術前で38 cells中37 cells(97%)が陽性、術後で16 cells中13 cells(81%)が陽性であった。N群CTCのNACRT前/後/術後での発現率は各々、4 cells中2 cells(50%)が陽性、28 cells中27 cells(96%)が陽性、2 cells中1 cell(50%)が陽性であった。【結語】v-CTC検出は有意な予後マーカーで、CTC上にはPD-L1が高率に発現し免疫チエックポイント阻害剤の有効性が期待できる。

Research Products

• [Journal Article] Prolonged Neoadjuvant Therapy for Locally Advanced Pancreatic Cancer. (2018)
  • Author(s): Eguchi H, Yamada D, Iwagami Y, Gotoh K, Kawamoto K, Wada H, Asaoka T, Noda T, Takeda Y, Tanemura M, Sakai D, Satoh T, Kudo T, Isohashi F, Mori M, Doki Y.
  • Journal Title: Dig Surg. Volume: 35 Pages: 70-76
  • DOI: 10.1159/000475477
  • Peer Reviewed / Open Access
• [Journal Article] The role of histone deacetylase 1 in distant metastasis of pancreatic ductal cancer. (2018)
  • Author(s): Shinke G, Yamada D, Eguchi H, Iwagami Y, Asaoka T, Noda T, Wada H, Kawamoto K, Gotoh K, Kobayashi S, Takeda Y, Tanemura M, Mori M, Doki Y.
  • Journal Title: Cancer Sci. Volume: 109 Pages: 2520-2531
  • DOI: 10.1111/cas.13700
  • Peer Reviewed / Open Access
• [Journal Article] Possible involvement of Enterococcus infection in the pathogenesis of chronic pancreatitis and cancer. (2018)
  • Author(s): Maekawa T, Fukaya R, Takamatsu S, Itoyama S, Fukuoka T, Yamada M, Hata T, Nagaoka S, Kawamoto K, Eguchi H, Murata K, Kumada T, Ito T, Tanemura M, Fujimoto K, Tomita Y, Tobe T, Kamada Y, Miyoshi E.
  • Journal Title: Biochem Biophys Res Commun. Volume: 506 Pages: 962-969
  • DOI: 10.1016/j.bbrc.2018.10.169
  • Peer Reviewed / Open Access
• [Journal Article] Impact of endoscopic stent insertion on detection of viable circulating tumor cells for obstructive colorectal cancer. (2018)
  • Author(s): Yamashita S, Tanemura M, Sawada G, Moon JH, Shimizu Y, Yamaguchi T, Kuwai T, Urata Y, Kuraoka K, Hatanaka N, Yamashita Y, Taniyama K.
  • Journal Title: Oncology Letters. Volume: 15 Pages: 400-406
  • DOI: 10.3892/ol.2017.7339
  • Peer Reviewed / Open Access
• [Journal Article] Hypoxia-Induced PLOD2 is a Key Regulator in Epithelial-Mesenchymal Transition and Chemoresistance in Biliary Tract Cancer. (2018)
  • Author(s): Okumura Y, Noda T, Eguchi H, Sakamoto T, Iwagami Y, Yamada D, Asaoka T, Wada H, Kawamoto K, Gotoh K, Kobayashi S, Takeda Y, Tanemura M, Umeshita K, Doki Y, Mori M.
  • Journal Title: Ann Surg Oncol. Volume: 25 Pages: 3728-3737
  • DOI: 10.1245/s10434-018-6670-8
  • Peer Reviewed / Open Access
• [Journal Article] Primary Intrahepatic Squamous Cell Carcinoma with Histological Collision of Adenocarcinoma and Squamous Cell Carcinoma: A Case Report. (2018)
  • Author(s): Tamaoka K, Tanemura M, Furukawa K, Mikamori M, Saito T, Ohtsuka M, Suzuki Y, Tei M, Kishi K, Yasuoka H, Tsujimoto M, Akamatsu H.
  • Journal Title: Am J Case Rep. Volume: 19 Pages: 1184-1191
  • DOI: 10.12659/AJCR.910676
  • Peer Reviewed / Open Access
• [Journal Article] Clinical Impact of Preoperative Sarcopenia on the Postoperative Outcomes After Pancreas Transplantation (2018)
  • Author(s): Fukuda Y, Asaoka T, Eguchi H, Sasaki K, Iwagami Y, Yamada D, Noda T, Kawamoto K, Gotoh K, Kobayashi S, Ito T, Takeda Y, Tanemura M, Mori M, Doki Y.
  • Journal Title: World J Surg. Volume: 42 Pages: 3364-3371
  • DOI: 10.1007/s00268-018-4639-1
  • Peer Reviewed / Open Access
• [Journal Article] Vitamin D Supplementation is a Promising Therapy for Pancreatic Ductal Adenocarcinoma in Conjunction with Current Chemoradiation (2018)
  • Author(s): Mukai Y, Yamada D, Eguchi H, Iwagami Y, Asaoka T, Noda T, Kawamoto K, Gotoh K, Kobayashi S, Takeda Y, Tanemura M, Mori M, Doki Y.
  • Journal Title: Ann Surg Oncol. Volume: 25 Pages: 1868-1879
  • DOI: 10.1245/s10434-018-6431-8
  • Peer Reviewed
• [Presentation] 切除可能膵癌におけるviabilityを加味した新規術中腹腔洗浄細胞診断の意義 (2018)
  • Author(s): 種村匡弘、古川健太、三賀森 学、岸 健太郎、西塔拓郎、大塚正久、鈴木陽三、
  • Organizer: 第118回日本外科学会定期学術集会
  • Invited
• [Presentation] A practical strategy to pancreatic cancer immunotherapy using resected human lysate vaccines remodeled to express α-gal epitopes (2018)
  • Author(s): Masahiro Tanemura, Kenta Furukawa, Eiji Miyoshi, Hidetoshi Eguchi, Hiroaki Nagano, Katsuyoshi Matsunami, Satoshi Nagaoka, Kentaro Kishi, Hiroki Akamatsu, Masaki Mori, Yuichiro Doki
  • Organizer: American Association for Cancer Research Annual Meeting 2018
  • Int'l Joint Research
• [Presentation] 切除可能膵癌におけるviabilityを加味した微小循環癌細胞の検出と予後予測、治療選択への応用 (2018)
  • Author(s): 種村匡弘、古川健太、三賀森 学、西塔拓郎、大塚正久、鈴木陽三、鄭 充善、岸 健太郎、浦田泰生、赤松大樹
  • Organizer: 第73回日本消化器外科学会総会
• [Presentation] Presence of viable-peritoneal tumor cells in peritoneal lavage fluid is a prognostic factor in pancreatic cancer (2018)
  • Author(s): Masahiro Tanemura, Kenta Furukawa, Manabu Mikamori, Kentaro Kishi, Takurou Saito, Masahisa Otuska, Yozo Suzuki, Yasuo Urata, Hiroki Akamatsu
  • Organizer: 第77回日本癌学会学術総会
• [Presentation] Endoscopic Stent Insertion for Obstructive Colorectal Cancer may induce Tumor Cell Dissemination into the Peripheral Circulation, resulting viable Circulating Tumor Cell Detection (2018)
  • Author(s): Shinya Yamashita, Masahiro Tanemura, Yosuke Shimizu, Toshio Kuwai, Yasuo Urata, kiyomi Taniyama
  • Organizer: American Association for Cancer Research Annual Meeting 2018
  • Int'l Joint Research
• [Presentation] Prognostic impact of modified telomerase-specific adenovirus-based identification of viable-peritoneal tumor cells in peritoneal lavage fluid in the patients with potentially resectable pancreatic cancer (2018)
  • Author(s): Masahiro Tanemura, Kenta Furukawa, Manabu Mikamori, Hiroki Akamatsu
  • Organizer: 第30回日本肝胆膵外科学会学術集会