Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Ablation of T cell–associated PD-1H enhances functionality and promotes adoptive immunotherapy
Li Hu, … , Gangxiong Huang, Lieping Chen
Li Hu, … , Gangxiong Huang, Lieping Chen
Published December 14, 2021
Citation Information: JCI Insight. 2022;7(2):e148247. https://doi.org/10.1172/jci.insight.148247.
View: Text | PDF
Research Article Immunology Therapeutics

Ablation of T cell–associated PD-1H enhances functionality and promotes adoptive immunotherapy

  • Text
  • PDF
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.

Authors

Li Hu, Ling Chen, Zexiu Xiao, Xu Zheng, Yuangui Chen, Na Xian, Christina Cho, Liqun Luo, Gangxiong Huang, Lieping Chen

×

Full Text PDF | Download (6.39 MB)


Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts