Development of algorithms for appropriate dosing intervals and durations of immune checkpoint inhibitors and avoidance of adverse events

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K16391
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Saitama Medical University
• Principal Investigator: Hashimoto Kosuke 埼玉医科大学, 医学部, 助教 (10866180)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 非小細胞肺癌 / ニボルマブ / ペムブロリズマブ / 末梢血単核細胞 / PET検査

Outline of Final Research Achievements

Immune checkpoint inhibitors impose a heavy socioeconomic burden, and their side effects are extremely difficult to predict and respond to. T-cell analysis of peripheral blood showed that PFS (progression-free survival) correlated with CD62L low CD4T cell percentage, and we focused on dosing intervals and avoidance of immune-related adverse events to see if a patient-specific treatment could be constructed. However, the expansion of the dosing interval was achieved by increasing the dose of the drug during the study period. CD62L low CCR4- CCR6+ CD4T cells were identified from the CD4T cell cluster and correlated with PFS and OS (overall survival). The correlation with PFS and OS was also confirmed by adding various metrics to FDG-PET.

Free Research Field

肺癌

Academic Significance and Societal Importance of the Research Achievements

PD-1阻害薬投与前の末梢血中のCD4+メタクラスターが腫瘍微小環境におけるCD4 T細胞浸潤と相関し、一方で末梢血中のTh1は局所CD8 T細胞浸潤と相関していた。また、抗腫瘍免疫に関与するCD4 T細胞クラスターからTh1やTh17と異なるCD62L low CCR4- CCR6+ CD4T細胞が同定され、PFS(無増悪生存期間)やOS(全生存期間)に相関していた。加えて、FDG-PETにMTV,TLG, 視覚的評価の解析を加えることで、PFSやOSとの相関を示すことができた。一般臨床でで得られる情報に追加の解析を加えることで、治療予測が立てられ医療経済に好影響を与えられる可能性がある。