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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 mak.s 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 check.oint block.de and found that natural k.ller cell granule protein-7(Nk.7) gene expression was decreased in non-responding patients. Functional assays revealed that reduced Nk.7 levels compromised cytolytic granule localization and release. Furthermore, transfection of CD8+ T cells with Nk.7 mRNA promoted tumor cell k.lling both in vitro and in vivo. Thus, we identify Nk.7 as critical for response to anti-PD-1 treatment, demonstrate the efficacy of Nk.7 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 Nk.7 scRNA-seq

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Paradox-driven adventures in the development of cancer immunology and immunotherapy

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Genes & Diseases 2019年第3期6卷 224-231页

作者： Whitney Barham joanina k.gicobi Yiyi Yan Roxana S.Dronca Haidong Dong Mayo Clinic Medical Scientist Training Program Mayo ClinicRochesterMNUSA Mayo Clinic Graduate School of Biomedical Sciences Mayo ClinicRochesterMNUSA Department of Immunology Mayo ClinicRochesterMNUSA Department of Urology Mayo ClinicRochesterMNUSA Department of Medical Oncology Mayo ClinicRochesterMNUSA Division of Hematology and Medical Oncology Mayo ClinicJacksonvilleFLUSA

After more than one hundred years of documented trials,immunotherapy has become a standard of care in the treatment of human *** of the k.owledge that led to recent break.hroughs seems quite logical from today’s point of ***,what we now cite as facts were originally considered paradoxes,meaning something contrary to expectations or perceived opinion at the *** order to mak. gains in the field of immunotherapy,one had to be willing to confront ideas and concepts that seemed to contradict one another,and reconcile how each could be *** is what led to new k.owledge and ***,we highlight some of these paradoxes and the milestone discoveries that followed,each one critical for our understanding of immune check.oint *** outlining some of the steps that we took.and the challenges that we overcame,we hope to inspire and encourage future generations of researchers to confront the paradoxes that still permeate the field.

关键词： Biomark.r Cancer immunotherapy Cytotoxic T cells Hyperprogression Immune check.oints PD-L1 PD-1

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Nk.7 mRNA therapy increases the anti-tumor cytotoxicity of CD8+ T cells and improves response to immune check.oint 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 mak.s 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 check.oint block.de and found that natural k.ller cell granule protein-7(Nk.7) gene expression was decreased in non-responding patients. Functional assays revealed that reduced Nk.7 levels compromised cytolytic granule localization and release. Furthermore, transfection of CD8 T cells with Nk.7 mRNA promoted tumor cell k.lling both in vitro and in vivo. Thus, we identify Nk.7 as critical for response to anti-PD-1 treatment, demonstrate the efficacy of Nk.7 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 Nk.7

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