Immunomodulatory effects of cryoablation combined with immune checkpoint inhibitors

• Project/Area Number: 18K16429
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55040:Respiratory surgery-related
• Research Institution: Teikyo University
• Principal Investigator: Yamauchi Yoshikane 帝京大学, 医学部, 講師 (30445390)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 凍結療法 / 肺癌 / 免疫療法 / MDSC / 骨髄由来抑制細胞 / 腫瘍周囲環境 / 腫瘍免疫

Outline of Final Research Achievements

We specifically addressed myeloid-derived suppressor cells (MDSCs) and T-cell immunity, which are thought to play an important role in the formation of the tumor microenvironment. We investigated their role in tumor immunomodulation both in the tumor itself and in the tumor surrounding environment when combined with cryoablation and ICIs. Our findings suggest that the combination of cryoablation and ICI might have synergetic anti-tumor effects, which could be evaluated by monitoring of MDSCs and T-cell immunity.

Academic Significance and Societal Importance of the Research Achievements

腫瘍の微小環境形成に重要な役割を果たすと考えられている骨髄由来抑制細胞（MDSC）とT細胞免疫について、凍結融解術とICIを組み合わせた場合の腫瘍自身と腫瘍周辺環境における免疫調節の役割について検討しました。その結果、凍結融解術とICIの併用は相乗的な抗腫瘍効果をもたらす可能性があり、その効果はMDSCsとT細胞免疫のモニタリングによって評価できることが示唆された。

Research Products

• [Journal Article] Circulating Interleukin-4 Is Associated with a Systemic T Cell Response against Tumor-Associated Antigens in Treatment-Na?ve Patients with Resectable Non-Small-Cell Lung Cancer (2020)
  • Author(s): Safi Seyer、Yamauchi Yoshikane、Hoffmann Hans、Weichert Wilko、Jost Philipp J.、Winter Hauke、Muley Thomas、Beckhove Philipp
  • Journal Title: Cancers Volume: 12 Issue: 12 Pages: 3496-3496
  • DOI: 10.3390/cancers12123496
  • Peer Reviewed / Open Access
• [Journal Article] Bone marrow expands the repertoire of functional T cells targeting tumor-associated antigens in patients with resectable non-small-cell lung cancer (2019)
  • Author(s): Safi Seyer、Yamauchi Yoshikane、Stamova Slava、Rathinasamy Anchana、op den Winkel Jan、J?nger Simone、Bucur Mariana、Umansky Ludmilla、Warth Arne、Herpel Esther、Eichhorn Martin、Winter Hauke、Hoffmann Hans、Beckhove Philipp
  • Journal Title: OncoImmunology Volume: 8 Issue: 12 Pages: e1671762-e1671762
  • DOI: 10.1080/2162402x.2019.1671762
  • Peer Reviewed / Open Access
• [Journal Article] Circulating and Tumor Myeloid-derived Suppressor Cells in Resectable Non?Small Cell Lung Cancer (2018)
  • Author(s): Yamauchi Yoshikane、Safi Seyer、Blattner Carolin、Rathinasamy Anchana、Umansky Ludmila、Juenger Simone、Warth Arne、Eichhorn Martin、Muley Thomas、Herth Felix J. F.、Dienemann Hendrik、Platten Michael、Beckhove Philipp、Utikal Jochen、Hoffmann Hans、Umansky Viktor
  • Journal Title: American Journal of Respiratory and Critical Care Medicine Volume: 198 Issue: 6 Pages: 777-787
  • DOI: 10.1164/rccm.201708-1707oc
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Immunomodulatory effects of cryoablation combined with immune checkpoint inhibitors in a murine lung cancer model (2022)
  • Author(s): Yoshikane Yamauchi, Yasuto Yamamoto, Yuichi Saito, Fumi Yokote, Hitoshi Dejima, Yukinori Sakao, Masafumi Kawamura
  • Organizer: IASLC 2022 WCLC World Conference on Lung Cancer
  • Int'l Joint Research