Identification of the secondary mechanism for immune evasion in cancer at the immune checkpoint inhibition

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K07171
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Kyushu University
• Principal Investigator: Kanae Yumimoto 九州大学, 生体防御医学研究所, 特別研究員 (30596838)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 免疫チェックポイント

Outline of Final Research Achievements

We tried to compare between "susceptible" and "resistant" cancers for the inhibition of PD-1/PD-L1 pathway, and attempted to describe a second immune checkpoint avoidance pathway by elucidating the differences. We found that we can uses B16F1 and B16F10 melanoma cells as a model of "susceptible" and "resistant" cancers for the inhibition of PD-1/PD-L1 pathway when transplanted via spleen. Mutagenesis and RNAseq analysis were performed after mutagenesis of PD-L1-deficient B16F1 cells, which were transformed to the PD-1/PD-L1 pathway "resistant cancer". By comparing the results from mouse with those of human immune checkpoint-sensitive and resistant patients, a total of 24 molecules were deduced as candidate master factors for the second avoidance mechanism from cancer immunity.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

近年、免疫チェックポイント阻害剤の明確な治療効果が示され、国内でも悪性黒色腫や非小細胞肺がんで承認されるなど、ますます注目を集めている。しかし、多くのがんにおいて奏効率は10％～30％程度であり、さらなる向上が求められている。同時に、抗体医薬を用いた治療はその高額な薬価が社会問題になっており、治療が有効な患者を選択するためのバイオマーカーの発見が必要とされている。本研究は、併用療法の最適化および新規バイオマーカー発見といった免疫チェックポイント阻害療法の拡充プロセスへ必須であると考える。