A co-culture model to study modulators of tumor immune evasion through scalable arrayed CRISPR-interference screens.

ABSTRACT: Cancer cells effectively evade immune surveillance, not only through the well-known PD-1/PD-L1 pathway but also via alternative mechanisms that impair patient response to immune checkpoint inhibitors. We present a novel co-culture model that pairs a reporter T-cell line with different melanoma cell lines that have varying immune evasion characteristics. We developed a scalable high-throughput lentiviral arrayed CRISPR interference (CRISPRi) screening protocol to conduct gene perturbations in both T-cells and melanoma cells, enabling the identification of genes that modulate tumor immune evasion. Our study functionally validates the co-culture model system and demonstrates the performance of the CRISPRi-screening protocol by modulating the expression of known regulators of tumor immu

SUBMITTER: Martinez R 

PROVIDER: S-EPMC11532180 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature