A5072061907- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- interferon and immune responses
- T-cell and B-cell Immunology
- DNA Repair Mechanisms
- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- Ubiquitin and proteasome pathways
- Cancer-related Molecular Pathways
- Cell death mechanisms and regulation
University of Alberta
2020-2025
Colorectal cancers (CRCs) deficient in DNA mismatch repair (dMMR) contain abundant CD8+ tumor-infiltrating lymphocytes (TILs) responding to the neoantigens from their unstable genomes. Priming of such tumor-targeted TILs first requires recruitment T cells into tumors, implying that this is an essential prerequisite successful dMMR anti-tumor immunity. We have discovered selective and activation systemic CRCs strictly depend on overexpression CCL5 CXCL10 due endogenous cGAS/STING type I IFN...
DNA damage caused by genetic instability or extrinsic treatment can induce leakage from the nucleus mitochondria into cytosol and activate innate adaptive immunity. To enable characterization of these endogenous cytosolic DNAs mechanisms that produce them, we developed an approach for isolation with no detectable mitochondrial contamination. Here describe compartment separation followed purification colorectal cancer cells illustrate how this may be expanded to other cell types.
Abstract Patients with microsatellite instable (MSI) colorectal cancers (CRC) face better prognosis than those the more common chromosomal (CIN) subtype due to improved anti-tumor immune responses characterized by high cytotoxic T cell infiltration. Previous investigation identified cytosolic DNA (cyDNA) sensor STING as necessary for chemokine-mediated recruitment in MSI CRCs. Here, we find cyDNA from CRC cells is inherently capable of inducing activation and induces dendritic (DCs)....
Summary Tumor heterogeneity poses a significant challenge in combating treatment resistance. Despite Polo-like kinase 1 (PLK1) being universally overexpressed cancers and contributing to chromosomal instability (CIN), direct PLK1 inhibition hasn’t yielded clinical progress. To address this, we utilized the synthetic dosage lethality (SDL) approach, targeting PLK1’s genetic interactions for selective killing of tumor cells while mitigating heterogeneity-associated challenges. Employing...
Summary Colorectal cancers (CRCs) deficient in DNA mismatch repair (dMMR) are heavily infiltrated by CD8+ tumor infiltrating lymphocytes (TILs) and associated with a better prognosis than the majority of CRCs. The immunogenicity dMMR CRCs is commonly attributed to abundant neoantigen generation due their extreme genomic instability. However, lack neoantigenic overlap between these other necessitates study antigen-independent mechanisms immune activation order identify therapeutic strategies...