A High-Throughput Immune-Oncology Screen Identifies EGFR Inhibitors as Potent Enhancers of Antigen-Specific Cytotoxic T-lymphocyte Tumor Cell Killing.

ABSTRACT: We developed a screening assay in which luciferized ID8 expressing OVA was cocultured with transgenic CD8⁺ T cells specifically recognizing the model antigen in an H-2b-restricted manner. The assay was screened with a small-molecule library to identify compounds that inhibit or enhance T cell-mediated killing of tumor cells. Erlotinib, an EGFR inhibitor, was the top compound that enhanced T-cell killing of tumor cells. Subsequent experiments with erlotinib and additional EGFR inhibitors validated the screen results. EGFR inhibitors increased both basal and IFNγ-induced MHC class-I presentation, which enhanced recognition and lysis of tumor cell targets by CD8⁺ cytotoxic T lymphocytes. The ID8 cell line was also transduced to constitutively express Cas9, and a pooled C

SUBMITTER: Lizotte PH 

PROVIDER: S-EPMC6601346 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature