Interferon Receptor Signaling Pathways Regulating PD-L1 and PD-L2 Expression
University of California, Los Angeles · Instituto de Salud Carlos III · +7 more institutions
Abstract
PD-L1 and PD-L2 are ligands for the PD-1 immune inhibiting checkpoint that can be induced in tumors by interferon exposure, leading to immune evasion. This process is important for immunotherapy based on PD-1 blockade. We examined the specific molecules involved in interferon-induced signaling that regulates PD-L1 and PD-L2 expression in melanoma cells. These studies revealed that the interferon-gamma-JAK1/JAK2-STAT1/STAT2/STAT3-IRF1 axis primarily regulates PD-L1 expression, with IRF1 binding to its promoter. PD-L2 responded equally to interferon beta and gamma and is regulated through both IRF1 and STAT3, which bind to the PD-L2 promoter. Analysis of biopsy specimens from patients with melanoma confirmed…
Citation impact
- FWCI
- 60.76
- Percentile
- 100%
- References
- 53
Authors
19- ÁGÁngel García-DíazCorresponding
University of California, Los Angeles
- DSDaniel Sanghoon Shin
University of California, Los Angeles
- BHBlanca Homet Moreno
University of California, Los Angeles, Instituto de Salud Carlos III, Translational Research in Oncology, Southern California Clinical and Translational Science Institute
- JDJustin D. Saco
University of California, Los Angeles
- HEHelena Escuin-Ordinas
University of California, Los Angeles
Topics & keywords
- Signal transduction
- Interferon
- Cell biology
- Receptor
- Chemistry
- PD-L1
- Biology
- Immune system
- Good health and well-being
Funding
- AAAmerican Association for Cancer ResearchAwards: 5T32AR058921-05, 5T32CA009120-39, 5T32CA009297-30
- CRCancer Research InstituteAward: SU2C-AACR-DT1012
- EIEntertainment Industry Foundation
- TCTower Cancer Research FoundationAwards: 5T32CA009297-30, G83727016, 5T32CA009120-39, 5T32AR058921-05
- PIParker Institute for Cancer ImmunotherapyAward: R35 CA197633
- RFRessler Family Foundation
- NINational Institutes of HealthAwards: P30DK41301, CA-16042, CA197633, R35 CA197633, P01 CA168585, AI-28697, SU2C-AACR-DT1012
- UOUniversity of California, Los Angeles
- CFCenter for AIDS Research, University of Washington
- SUStand Up To CancerAwards: 5T32CA009297-30, SU2C-AACR-DT1012), SU2C-AACR-DT1012, 5T32AR058921-05, 5T32CA009120-39
- JCJonsson Comprehensive Cancer Center
- DGDavid Geffen School of Medicine, University of California, Los AngelesAwards: 27163, CURE/P30DK41301-26
- UAUCLA AIDS Institute
- CFCenter for AIDS Research, University of California Los Angeles
- CNCalifornia NanoSystems Institute