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Trp53 Mutation-Mediated mTORC1 Inhibition and Inflammation Suppression Confer Resistance to Checkpoint Immunotherapy

GSE295668 Mus musculus Expression profiling by high throughput sequencing; Other 4 samples Submitted 2025/08/31 Platform GPL24247
Summary
p53 is a critical tumor suppressor gene that inhibits cancer development by regulating cell cycle arrest, apoptosis, DNA repair, and metabolism. However, recent studies examining TP53 mutations in cancer immunotherapy have yielded inconsistent results, likely due to differences in tumor mutational burden (TMB) and the context-dependent roles of specific p53 mutants. In this study, we assessed the function of G242V and S258I Trp53 mutations in MC38 cells in the context of immunotherapy by generating Trp53 deletion and observed significantly enhanced responses to anti-PD-1 therapy. We next characterized how the Trp53 deletion in MC38 tumor cells alters the immune response. To this end, we performed single-cell RNA and paired single-cell TCR sequencing (scRNAseq and scTCRseq) of anti-PD-1 treated Trp53CON and Trp53KO MC38 tumors on day 11 after tumor cells inoculation.
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Direct links to NCBI, no account and no request form: the whole study as GSE295668_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 4 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1255567 and SRA study SRP581365. Searching any of these in the dataset finder brings you back here.

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