NKG7 mRNA therapy increases the anti-tumor cytotoxicity of CD8+ T cells and improves response to immune checkpoint inhibitors
作者单位：The First Hospital of China Medical University Mayo Clinic Mayo Clinic College of Medicine and Science
会议名称：《2021年中国肿瘤标志物学术大会暨第十五届肿瘤标志物青年科学家论坛》
会议日期：2021年
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
关 键 词：cancer immunotherapy anti-PD-1 treatment scRNA-seq NKG7
摘 要：Translating information gained from single cell RNA-sequencing(scRNA-seq) analyses into clinical therapeutics remains a challenge. However, with the advent of technology that makes mRNA-based modulation of primary cells possible, targets identified in scRNA-seq datasets can now be manipulated directly. Here we model this approach in the context of cancer immunotherapy. We performed scRNA-seq analysis of peripheral CD8 T cells from patients who received anti-PD-1 checkpoint blockade and found that natural killer cell granule protein-7(NKG7) gene expression was decreased in non-responding patients. Functional assays revealed that reduced NKG7 levels compromised cytolytic granule localization and release. Furthermore, transfection of CD8 T cells with NKG7 mRNA promoted tumor cell killing both in vitro and in vivo. Thus, we identify NKG7 as critical for response to anti-PD-1 treatment, demonstrate the efficacy of NKG7 mRNA as a therapeutic strategy for improving cancer immunotherapy, and provide a model for translating scRNA-seq findings into mRNA-based therapy.