Language
English
Publication Date
1-1-2023
Journal
Frontiers in Immunology
DOI
10.3389/fimmu.2023.1274199
PMID
37928524
PMCID
PMC10623129
PubMedCentral® Posted Date
10-20-2023
PubMedCentral® Full Text Version
Post-print
Abstract
Folate receptor delta (FRδ) has been used as a biomarker for regulatory T cells (Tregs), because its expression is limited to Tregs and ovum. Although FRδ is unable to bind folate, we have used molecular docking software to identify a folate congener that binds FRδ with high affinity and have exploited this FRδ-specific ligand to target attached drugs (imaging agents, immune activators, and immune suppressors) specifically to Tregs in murine tumor xenografts. Analysis of treated tumors demonstrates that targeting of a Toll-like receptor 7 agonist inhibits Treg expression of FOXP3, PD-1, CTLA4, and HELIOS, resulting in 40-80% reduction in tumor growth and repolarization of other tumor-infiltrating immune cells to more inflammatory phenotypes. Targeting of the immunosuppressive drug dexamethasone, in contrast, promotes enhanced tumor growth and shifts the tumor-infiltrating immune cells to more anti-inflammatory phenotypes. Since Tregs comprise
Keywords
Humans, Animals, Mice, T-Lymphocytes, Regulatory, Molecular Docking Simulation, Neoplasms, Transcription Factors, Immunosuppressive Agents, Folic Acid, regulatory T cells, folate receptor-delta, tumor immunosuppression, immunomodulation, immunotherapy of cancer
Published Open-Access
yes
Recommended Citation
Alfar, Rami; Napoleon, John V; Shahriar, Imrul; et al., "Selective Reprogramming of Regulatory T Cells in Solid Tumors Can Strongly Enhance or Inhibit Tumor Growth" (2023). Faculty and Staff Publications. 1954.
https://digitalcommons.library.tmc.edu/baylor_docs/1954
Included in
Biological Phenomena, Cell Phenomena, and Immunity Commons, Life Sciences Commons, Medical Cell Biology Commons, Medical Microbiology Commons, Medical Molecular Biology Commons, Oncology Commons