PD-1 genetic fate mapping uncovers immune cell diversity mediating the efficacy of combined PD-1 blockade and chemotherapy - PubMed
4 days ago
- #immune cell diversity
- #combination therapy
- #PD-1 blockade
- PD-1 genetic fate mapping reveals immune cell diversity in combined PD-1 blockade and chemotherapy efficacy.
- Pdcd1-CreERT2 fate-mapping mice were used to trace PD-1-expressing cells during PD-1 blockade.
- PD-1-fate-mapped lymphocytes downregulated PD-1 in the spleen but retained it in tumors, except for NK cells.
- Single-cell transcriptional profiling identified 15 distinct immune clusters with treatment-dependent abundances.
- Combination therapy expanded cytotoxic CD8 T cells and a dysfunctional Treg cluster, enhancing CTL activity.
- PD-1 blockade synergizes with cytotoxic chemotherapy to diversify and expand PD-1 lineage-traced CTL clonotypes.
- The fate-mapping system is a valuable tool for identifying immune cells responsive to ICI therapy.