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Transcriptomic analyses of PDX tumors (QQX-17) to gain insight into the mechanisms underlying FOLFOXIRI-induced DTP state.

ABSTRACT: Chemotherapy resistance remains a significant challenge, often leading to tumor relapse and poor prognosis. While past efforts to overcome treatment resistance have focused primarily on genetic alterations—such as somatic mutations, chromosomal aberrations, and dysregulated signaling pathways—these insights have yet to translate into effective clinical interventions. The recent discovery of drug-tolerant persister (DTP) cells, which survive therapy through reversible, non-genetic adaptations akin to embryonic diapause, has unveiled a novel mechanism of chemotherapy resistance. To investigate this further, we employed treatment-naïve colorectal cancer (CRC) patient-derived xenograft (PDX) models. Upon reaching a tumor volume of 100 mm³, the PDX models were treated with a single maximum-tolerated dose of the FOLFOXIRI regimen. Post-treatment responses varied, including initial tumor shrinkage followed by regrowth, mirroring the "sensitivity-DTP-regrowth" pattern observed in CRC patients. Transcriptomic analyses of these PDX tumors were then conducted to elucidate the mechanisms underlying the FOLFOXIRI-induced DTP state.

ORGANISM(S): Homo sapiens

PROVIDER: GSE300623 | GEO | 2026/06/27

REPOSITORIES: GEO

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Transcriptomic analyses of PDX tumors (QQX-09) to gain insight into the mechanisms underlying FOLFOXIRI-induced DTP state.

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2023-01-02 | PXD036517 | Pride

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Project description:Diphtheria, tetanus, and pertussis (DTP) are infectious diseases caused by toxin-producing bacteria that can be fatal, especially in children. Despite the availability of combined DTP vaccines for more than 60 years, a comprehensive understanding of how human antibodies respond to DTP vaccination, which helps further improve the vaccine remains elusive. Here, we aimed to characterize toxin-specific antibody repertoires following DTP vaccination. To this end, CD19+CD27+ antigen-experienced B cells obtained from four healthy donors 7-days post vaccination were sorted for toxin-binding and non-toxin-binding B cells, using each of the DTP recombinant toxins (DT, TT, and PT) as fluorescent bait. 10X single-cell immune profiling was then performed, followed by in silico antibody sequence clustering.

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