Elucidation of immune system and search for innovative biomarkers in peritoneal dissemination of gastric cancer

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K18095
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kumamoto University
• Principal Investigator: KIYOZUMI Yuuki 熊本大学, 病院, 非常勤診療医師 (30827324)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 胃癌 / 免疫寛容 / 免疫チェックポイント阻害薬 / 不均一性

Outline of Final Research Achievements

PD-L1 expression as a predictive biomarker for PD-1 inhibitor efficacy in gastric cancer (GC) remains controversial. Firstly, PD-L1 expressions in biopsy and paired resected samples by IHC staining were compared according to the number of biopsies. Single biopsy showed a lower accordance rate compared with multiple biopsies. Therefore, Multiple biopsies are recommended for accurate diagnosis of PD-L1 expression in GC. Secondly, we aimed to elucidate the effects of trastuzumab (Tmab) on PD-L1 expression in GC. PD-L1 expression was upregulated by Tmab in HER2-amplified GC cell lines co-cultured with peripheral blood mononuclear cells. PD-L1 upregulation by Tmab was also observed in the GC cells co-cultured with NK cells in time-dependent manner, but not with monocytes. Tmab can upregulate PD-L1 expression on GC cells through interaction with NK cells. These results suggest clinical implications in the assessment of predictive significance of PD-L1 expression for PD-1 inhibitors.

Free Research Field

消化器外科分野における消化管悪性腫瘍

Academic Significance and Societal Importance of the Research Achievements

胃癌に対する免疫チェックポイント阻害薬の効果を予測するうえで重要と考えられる、免疫関連因子の発現の空間的不均一性、経時的不均一性を評価するために、本研究を行った。その結果、複数回の生検を行わないと免疫関連因子の発現を正確に評価できないことや、化学療法が発現に影響与えることを証明できたため、今後の臨床における治療予測因子として重要な役割を果たすと考えられる。