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NKG7 mRNA therapy increases the anti-tumor cytotoxicity of CD8+ T cells and improves response to immune checkpoint inhibitors

NKG7 mRNA therapy increases the anti-tumor cytotoxicity of C...

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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

作者： Ti Wen Whitney Barham Ying Li Henan Zhang Joanina K.Gicobi Jacob B.Hirdler Xin Liu hyoungjun ham Fabrice Lucien Daniel D.Billadeau Haidong Dong The First Hospital of China Medical University Mayo Clinic Mayo Clinic College of Medicine and Science

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.

关键词： cancer immunotherapy anti-PD-1 treatment scRNA-seq NKG7

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NKG7 mRNA therapy increases the anti-tumor cytotoxicity of CD8+ T cells and improves response to immune checkpoint inhibitors

NKG7 mRNA therapy increases the anti-tumor cytotoxicity of C...

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第十四届全国免疫学学术大会

作者： Ti Wen Whitney Barham Ying Li Henan Zhang Joanina K. Gicobi Jacob B. Hirdler Xin Liu hyoungjun ham Fabrice Lucien Hu Li Daniel D. Billadeau Haidong Dong Department of Medical Oncology the First Hospital of China Medical University Mayo Clinic Mayo Clinic College of Medicine and Science

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.

关键词： Cancer Immunotherapy anti-PD-1 response NKG7 scRNA-seq

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