Publications by authors named "Chris Silvin"
Background: As heterogeneous tumors develop in the face of intact immunity, tumor cells harboring genomic or expression defects that favor evasion from T-cell detection or elimination are selected. For patients with such tumors, T cell-based immunotherapy alone infrequently results in durable tumor control.
Methods: Here, we developed experimental models to study mechanisms of T-cell escape and demonstrated that resistance to T-cell killing can be overcome by the addition of natural killer (NK) cells engineered to express a chimeric antigen receptor (CAR) targeting programmed death ligand-1 (PD-L1).
Article Synopsis
- Researchers studied how a drug called SX-682 can stop certain immune cells (MDSCs) from getting into tumors and help fight cancer better.
- They found that a type of MDSC, called PMN-MDSCs, was very common in the tumors and made it harder for other immune cells, like T cells, to do their job.
- Using SX-682 helped reduce the number of PMN-MDSCs in the tumors, which made the T cells work better and could improve treatments for cancer patients.
Checkpoint inhibitors are relatively inefficacious in head and neck cancers, despite an abundance of genetic alterations and a T-cell-inflamed phenotype. One significant barrier to efficacy may be the recruitment of myeloid-derived suppressor cells (MDSC) into the tumor microenvironment. Here we demonstrate functional inhibition of MDSC with IPI-145, an inhibitor of PI3Kδ and PI3Kγ isoforms, which enhances responses to PD-L1 blockade.
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