Journal article
Ablation of T cell–associated PD-1H enhances functionality and promotes adoptive immunotherapy
JCI insight, Vol.7(2), e148247
01/25/2022
DOI: 10.1172/jci.insight.148247
PMCID: PMC8855794
PMID: 34905507
Abstract
Programmed death-1 homolog (PD-1H) is a coinhibitory molecule that negatively regulates T cell–mediated immune responses. In this study, we determined whether ablation of T cell–associated PD-1H could enhance adoptive T cell therapy in experimental tumor models. The expression of PD-1H is upregulated in activated and tumor-infiltrating CD8
+
T cells. Activated CD8
+
T cells from PD-1H–deficient (PD-1H–KO) mice exhibited increased cell proliferation, cytokine production, and antitumor activity in vitro. Adoptive transfer of PD-1H–KO CD8
+
T cells resulted in the regression of established syngeneic mouse tumors. Similar results were obtained when PD-1H was ablated in T cells by CRISPR/Cas9-mediated gene silencing. Furthermore, ablation of PD-1H in CAR-T cells significantly improved their antitumor activity against human xenografts in vivo. Our results indicate that T cell–associated PD-1H could suppress immunity in the tumor microenvironment and that targeting PD-1H may improve T cell adoptive immunotherapy.
Details
- Title: Subtitle
- Ablation of T cell–associated PD-1H enhances functionality and promotes adoptive immunotherapy
- Creators
- Li Hu - Sun Yat-sen UniversityLing Chen - Fujian Medical UniversityZexiu Xiao - Sun Yat-sen UniversityXu Zheng - Sun Yat-sen UniversityYuangui Chen - Union HospitalNa Xian - Fujian Medical UniversityChristina Cho - Yale UniversityLiqun Luo - Fujian Medical UniversityGangxiong Huang - Fujian Medical UniversityLieping Chen - Yale University
- Resource Type
- Journal article
- Publication Details
- JCI insight, Vol.7(2), e148247
- DOI
- 10.1172/jci.insight.148247
- PMID
- 34905507
- PMCID
- PMC8855794
- NLM abbreviation
- JCI Insight
- ISSN
- 2379-3708
- eISSN
- 2379-3708
- Publisher
- American Society for Clinical Investigation
- Grant note
- 2019YFC1316102 / National Key Research and Development Program 2020J01657 / ; 2016sysbz02 / National Collaboration Center in Immuno-Oncology Program 2011Y035 / Guangdong Province Innovative Research Program 2016L3006,2015Y2002 / Fujian Province Department of Science and Technology Research Program
- Language
- English
- Date published
- 01/25/2022
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984949218802771
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