A5093100661- Immune cells in cancer
- Immune Cell Function and Interaction
- Atherosclerosis and Cardiovascular Diseases
- Single-cell and spatial transcriptomics
- Reproductive System and Pregnancy
- CAR-T cell therapy research
- T-cell and B-cell Immunology
Palo Alto University
2024
Stanford University
2023-2024
The drivers of immune evasion are not entirely clear, limiting the success cancer immunotherapies. Here we applied single-cell spatial and perturbational transcriptomics to delineate in high-grade serous tubo-ovarian cancer. To this end, first mapped organization by profiling more than 2.5 million cells situ 130 tumors from 94 patients. This revealed a malignant cell state that reflects tumor genetics is predictive T natural killer infiltration levels response checkpoint blockade. We then...
SUMMARY Immune exclusion and evasion are central barriers to the success of immunotherapies cell therapies in solid tumors. Here we applied single spatial perturbational transcriptomics alongside clinical, histological, genomic profiling elucidate immune high-grade serous tubo-ovarian cancer (HGSC). Using high-plex profiled more than 1.3 million cells from 95 tumors 60 patients, revealing generalizable principles HGSC tumor tissue organization. Our data demonstrates that effector T resist...
Insufficient infiltration of cytotoxic lymphocytes to solid tumors limits the efficacy immunotherapies and cell therapies. Here, we report a programmable mechanism mobilize Natural Killer (NK) T cells breast cancer by engineering these express orphan metabolite-sensing G protein-coupled receptors (GPCRs). First, in vivo vitro CRISPR activation screens NK-92 identified GPR183, GPR84, GPR34, GPR18, FPR3, LPAR2 as top enhancers both tumor chemotaxis cancer. These genes equip NK with ability...
Abstract Immune exclusion and evasion are central barriers to the success of immunotherapies cell therapies in solid tumors. Here we applied single spatial perturbational transcriptomics alongside clinical,histological, genomic profiling elucidate immune high-grade serous tubo-ovarian cancer (HGSC). Using high-plex profiled more than 1.3 million cells from 95 tumors 60 patients, revealing generalizable principles HGSC tumor tissue organization.Our data demonstrates that effector T resist...
Abstract Cell autonomous resistance mechanisms can protect cancer cells from targeted T cell elimination, resulting in to a broad range of immunotherapies. High-throughput gene knockout and inhibition screens have been instrumental identifying key drivers such mechanisms, yet often uncovering activity that is essential but not sufficient for response. Here we set out leverage activation as an orthogonal approach identify novel regulators the cancer-immune interface. First, performed CRISPR...