Faculty, Staff and Student Publications
Publication Date
9-24-2024
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abstract
Understanding the mechanisms underlying immune evasion is crucial for developing novel anticancer modalities. To systematically uncover tumor-intrinsic genetic modulators involved in immune escape in tumor microenvironment, we performed genome-scale in vivo CRISPR screens in two syngeneic models and later expanded up to seven syngeneic models with a focused validation library. These data help us better understand tumor immune evasion and pave the way for developing effective therapeutics. Importantly, we uncovered that Mga depletion elicited an antitumor immune response and inhibited tumor growth in triple-negative breast cancer. Our findings suggest that Mga may play a role in modulating the tumor immune landscape, though the precise mechanisms require further investigation. Further studies are needed to test MGA inhibition in cancer treatment.
Keywords
Animals, Female, Humans, Mice, Cell Line, Tumor, Clustered Regularly Interspaced Short Palindromic Repeats, CRISPR-Cas Systems, Gene Expression Regulation, Neoplastic, Immunotherapy, Interferon-gamma, Triple Negative Breast Neoplasms, Tumor Escape, Tumor Microenvironment, CRISPR screen, breast cancer, in vivo screen, MGA, immune evasion
DOI
10.1073/pnas.2406325121
PMID
39298484
PMCID
PMC11441491
PubMedCentral® Posted Date
9-19-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Medical Genetics Commons, Oncology Commons