EBV抗原発現調節による、EBV関連胃癌に対する効果的ながん免疫療法の開発

2022 Fiscal Year Annual Research Report

• Project/Area Number: 22F21409
• Allocation Type: Single-year Grants
• Research Institution: Kyoto University
• Principal Investigator: 本庶 佑 京都大学, 医学研究科, 特任教授 (80090504)
• Co-Investigator(Kenkyū-buntansha): LEONG MAN LONG 京都大学, 医学研究科, 外国人特別研究員
• Project Period (FY): 2022-04-22 – 2024-03-31
• Keywords: scRNA-Seq / NK / EGFR / NSCLC

Outline of Annual Research Achievements

We collected 12 NSCLC patient samples of PBMC and tumor-infiltrating lymphocytes (TIL) to perform scRNA-Seq. From the result of TIL, we found that the proportion of total NK cells in the patients with EGFR-Mut is larger than that in the WT patients. However, the proportion of uNK (a suset of NK cells) in EGFR-WT patients is larger that in EGFR-Mut patients. We further establish a set of uNK signature genes which is positively associated with the expression of activation markers in CD8T cells. When studying the scRNA-Seq data of the patients PBMC, the NK cells express part of the uNK signature genes. Overall, these results suggest that uNK, at least in EGFR-WT NSCLC patients, may have a potiental role to support T-cell activation.

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

Although the content of the current project is slightly different from the original one, the progress is on track. Originally, we planned to finish the discovery phase in the first year. In this project, we have already finished the discovery phase by identifying a set of uNK signature genes associated with CD8T activation. We are currently in the validation phase examining the presence of uNK in the NSCLC tissues, and will move on to the functional studies once the validation phase is done.

Strategy for Future Research Activity

Originally, we planned to investigate a strategy to sensitize ICI-therapy on EBV-associated gastric cancer (GC). However, we found it difficult to recruit the specimens from GC patients and PBMC from healthy donors, especially during the outbreak of COVID-19 last year. Instead, we have some lung cancer specimens stored previously. Hence, we switch the cancer model from gastric to lung cancer, but the main focus of this project remains the same, that is studying how to improve the efficiency of ICI therpay. Currently, we have established a set of uNK signature genes associated with the activation of CD8 T cells. After validation of the presence of uNK in NSCLC tissues, we will study if an effective ICI therapy is dependent on the presence of uNK to support the CD8 T cells activation.