Antigen presentation by B cells enables epitope spreading across an MHC barrier
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ABSTRACT:
PROVIDER: PRJNA835703 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19117221_1.fastq.gz | Fastqsanger.gz | |||
| SRR19117221_2.fastq.gz | Fastqsanger.gz | |||
| SRR19117222_1.fastq.gz | Fastqsanger.gz | |||
| SRR19117222_2.fastq.gz | Fastqsanger.gz | |||
| SRR19117223_1.fastq.gz | Fastqsanger.gz |
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Project description:Loss of MHC class I (MHC-I) antigen presentation in cancer cells can lead to immunotherapy resistance. Using a genome-wide CRISPR/Cas9 screen we identify a critical role for polycomb repressive complex 2 (PRC2) in the coordinated transcriptional silencing of the MHC-I antigen processing pathway (MHC-I APP). This evolutionarily conserved function of PRC2 promotes evasion of T-cell mediated immunity, enabling tumor transmission to non-histocompatible recipients in small cell lung cancer (SCLC) and Tasmanian Devil Facial Tumor. MHC-I APP gene promoters in MHC-I low cancers harbour bivalent activating H3K4me3 and repressive H3K27me3 histone modifications, silencing basal MHC-I expression and restricting cytokine induced MHC-I APP gene upregulation. Bivalent chromatin at MHC-I APP genes is a normal developmental process active in embryonic stem cells and maintained during neural progenitor differentiation. This physiological silencing of MHC-I expression highlights a conserved mechanism by which cancers arising from these primitive tissues coopt PRC2 activity to enable immune evasion.
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