2021 Fiscal Year Final Research Report

Development of novel combination immunotherapy against lung cancer and mesothelioma: establishment of immunological basis for clinic

Research Project

PDF

Project/Area Number	19H03668
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 53030:Respiratory medicine-related
Research Institution	The University of Tokushima
Principal Investigator	NISHIOKA Yasuhiko 徳島大学, 大学院医歯薬学研究部(医学域), 教授 (70274199)
Co-Investigator(Kenkyū-buntansha)	軒原浩徳島大学, 大学院医歯薬学研究部(医学域), 准教授 (00505919) 佐藤正大徳島大学, 病院, 講師 (80530899) 三橋惇志徳島大学, 大学院医歯薬学研究部(医学域), 特任助教 (00833732)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	肺がん / がん免疫療法 / 線維細胞 / 骨髄由来抑制細胞 / 樹状細胞
Outline of Final Research Achievements	To develop novel combined immunotherapy against lung cancer and mesothelioma, we studied three immunomodulatory cells, such as fibrocytes, myeloid-derived suppressor cells (MDSC) and dendritic cells (DC) in tumors. We demonstrated that tumor-infiltrating fibrocytes played a role in tumor immunity as an antigen-presenting cells in situ. The combined therapy with anti-PD-L1 antibody and intratumoral administration of fibrocytes enhanced anti-tumor immunity. The cytotoxic drug, S-1, also enhanced anti-tumor immunity of anti-PD-1 antibody by inhibiting the accumulation of MDSC into tumors. In addition, combined therapy with anti-PD-1 antibody and intratumoral administration of DC was more effective in inhibiting tumor growth as compared to each monotherapy. These combinations will be novel and promising immunotherapies in the future.
Free Research Field	呼吸器内科学、がん免疫
Academic Significance and Societal Importance of the Research Achievements	本研究により動物モデルを用いて肺がん・中皮腫に対する効果的な3つの新たな複合がん免疫療法が提案された。これまでに抗原提示細胞として十分には認識されていない腫瘍内線維細胞（fibrocyte）に着目し、特に抗PD-L1抗体との併用下において抗腫瘍免疫増強に重要な役割を果たしていることの発見は、学術的意義が大きいことに加え、今後の新規複合がん免疫療法への展開という点では社会的意義も大きい。抗PD-1抗体と抗がん剤のS-1あるいは樹状細胞の腫瘍内投与という新たな複合がん免疫療法についても、現実的な複合がん免疫療法として今後の展開が期待されることから社会的意義は大きいと言える。