期刊
NATURE COMMUNICATIONS
卷 7, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms10501
关键词
-
资金
- Clinical Investigator Award from Damon Runyon Cancer Research Foundation
- Developmental Project Grant from NCI [P50 CA090578]
- Starr Consortium for Cancer Research
- NIH/NCI [P01 CA120964, 5R01CA163896-04, 1R01CA195740-01, 5R01CA140594-07, 5R01CA122794-10, 5R01CA166480-04]
- Gross-Loh Family Fund for Lung Cancer Research
- Susan Spooner Family Lung Cancer Research Fund at Dana-Farber Cancer Institute
- Margaret A. Cunningham Immune Mechanisms in Cancer Research Fellowship Award
- Kanae Foundation for the Promotion of Medical Science Fellowship Award
- Deutsche Forschungsgemeinschaft [HE 6897/1-1]
- Claudia Adams Barr Program for Innovative Cancer Research
- NIH [R01AI08995]
- American Cancer Society [RSG 11-186]
- NCI [CA090578]
- Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant [SU2C-AACR-DT17-15]
Despite compelling antitumour activity of antibodies targeting the programmed death 1 (PD-1): programmed death ligand 1 (PD-L1) immune checkpoint in lung cancer, resistance to these therapies has increasingly been observed. In this study, to elucidate mechanisms of adaptive resistance, we analyse the tumour immune microenvironment in the context of anti-PD-1 therapy in two fully immunocompetent mouse models of lung adenocarcinoma. In tumours progressing following response to anti-PD-1 therapy, we observe upregulation of alternative immune checkpoints, notably T-cell immunoglobulin mucin-3 (TIM-3), in PD-1 antibody bound T cells and demonstrate a survival advantage with addition of a TIM-3 blocking antibody following failure of PD-1 blockade. Two patients who developed adaptive resistance to anti-PD-1 treatment also show a similar TIM-3 upregulation in blocking antibody-bound T cells at treatment failure. These data suggest that upregulation of TIM-3 and other immune checkpoints may be targetable biomarkers associated with adaptive resistance to PD-1 blockade.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据