Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Physician-Scientist Development
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • In-Press Preview
    • Resource and Technical Advances
    • Clinical Research and Public Health
    • Research Letters
    • Editorials
    • Perspectives
    • Physician-Scientist Development
    • Reviews
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Resource and Technical Advances
  • Clinical Research and Public Health
  • Research Letters
  • Editorials
  • Perspectives
  • Physician-Scientist Development
  • Reviews
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Transfers
  • Advertising
  • Job board
  • Contact

Usage Information

TET2 promotes tumor antigen presentation and T cell IFN-γ, which is enhanced by vitamin C
Meng Cheng, … , Yue Xiong, Albert S. Baldwin
Meng Cheng, … , Yue Xiong, Albert S. Baldwin
Published October 10, 2024
Citation Information: JCI Insight. 2024;9(22):e175098. https://doi.org/10.1172/jci.insight.175098.
View: Text | PDF
Research Article Immunology Oncology

TET2 promotes tumor antigen presentation and T cell IFN-γ, which is enhanced by vitamin C

  • Text
  • PDF
Abstract

Immune evasion by tumors is promoted by low T cell infiltration, ineffective T cell activity directed against the tumor, and reduced tumor antigen presentation. The TET2 DNA dioxygenase gene is frequently mutated in hematopoietic malignancies and loss of TET enzymatic activity is found in a variety of solid tumors. We showed previously that vitamin C (VC), a cofactor of TET2, enhances tumor-associated T cell recruitment and checkpoint inhibitor therapy responses in a TET2-dependent manner. Using single-cell RNA sequencing (scRNA-seq) analysis performed on B16-OVA melanoma tumors, we have shown here that an additional function for TET2 in tumors is to promote expression of certain antigen presentation machinery genes, which is potently enhanced by VC. Consistently, VC promoted antigen presentation in cell-based and tumor assays in a TET2-dependent manner. Quantifying intercellular signaling from the scRNA-seq dataset showed that T cell–derived IFN-γ–induced signaling within the tumor and tumor microenvironment requires tumor-associated TET2 expression, which is enhanced by VC treatment. Analysis of patient tumor samples indicated that TET activity directly correlates with antigen presentation gene expression and with patient outcomes. Our results demonstrate the importance of tumor-associated TET2 activity as a critical mediator of tumor immunity, which is augmented by high-dose VC therapy.

Authors

Meng Cheng, Angel Ka Yan Chu, Zhijun Li, Shiyue Yang, Matthew D. Smith, Qi Zhang, Nicholas G. Brown, William F. Marzluff, Nabeel Bardeesy, J. Justin Milner, Joshua D. Welch, Yue Xiong, Albert S. Baldwin

×

Usage data is cumulative from October 2024 through August 2025.

Usage JCI PMC
Text version 2,212 357
PDF 472 66
Figure 430 0
Table 116 0
Supplemental data 233 29
Citation downloads 106 0
Totals 3,569 452
Total Views 4,021
Created with Highcharts 3.0.9MonthTotalOct 24Nov 24Dec 24Jan 25Feb 25Mar 25Apr 25May 25Jun 25Jul 25Aug 250k1k2k3k4k5k
JCI Citation downloads
JCI Figure
JCI Text version
JCI PDF
JCI Supplemental data
JCI Table
PMC Text version
Total JCI usage
Total PMC usage
Total usage

Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.

Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.

Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts