Single-cell-based identification of drug synergy with immunotherapy via tumor microenvironment remodeling - PubMed
5 hours ago
- #Drug Synergy
- #Tumor Microenvironment
- #Immunotherapy
- Single-cell RNA sequencing used to identify drug synergy with immunotherapy via tumor microenvironment (TME) remodeling.
- L1000 platform screened 739 immune-modulating compounds across various cancers.
- 12 distinct meta-programs associated with TME remodeling identified, including processes like antigen presentation and tissue repair.
- Myeloid-derived suppressor cells (MDSCs) found to play a key immunosuppressive role in TME.
- MP scoring algorithm developed to quantify TME responsiveness, identifying allopurinol as a potent enhancer of anti-PD-1 therapy.
- Combination of allopurinol and anti-PD-1 therapy led to significant tumor-free outcomes in vivo (4/6).
- Provides a robust framework for assessing TME remodeling and uncovering compounds that modulate immunotherapeutic efficacy.