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Multimodal blood based profiling reveals insights into mechanisms of immunotherapy resistance

ABSTRACT: Multimodal blood based profiling reveals insights into mechanisms of immunotherapy resistance

PROVIDER: PRJNA1256836 | ENA |

REPOSITORIES: ENA

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Multimodal blood based profiling reveals insights into mechanisms of immunotherapy resistance

Project description:Many cancer patients treated with immune checkpoint blockade (ICB) do not have durable treatment responses. Circulating biomarkers have the potential to identify patients with primary resistance or early progression on therapy to alter treatment course and avoid unnecessary toxicity. Unbiased multimodal proteomic profiling in blood has been underexplored due to the previously limited scalability of multiplexing technologies or cohorts lacking time-series sampling. To address this, we performed plasma proteomic profiling of >2,900 proteins and high-dimensional mass cytometry of peripheral blood lymphocytes across serial time points in 250 metastatic melanoma patients on ICB treatment. We further obtained 92 patient-matched tumor samples, which were processed for single-cell and/or bulk RNA sequencing. Proteins upregulated post-ICB were associated with inflammatory pathways involving the activation of effector immune functions. Expression of genes corresponding to these proteins was higher in immune cells involved in recruitment and tumor reactivity. Expression of genes corresponding to plasma proteins more abundant in non-responders was highest in suppressive myeloid subsets and malignant cells. We further posit the involvement of these non-responder genes in immunosuppressive and pro-tumor interactions, which we confirmed using publicly available spatial transcriptomic data. We also found that epithelial-specific proteins in the circulation of responders post-ICB correlate with patient toxicity and likely originate from healthy tissues. Together, these data represent one of the deepest peripheral biomarker studies using paired blood and tumor samples in melanoma patients treated with ICB, and begin to elucidate the complex interplay between tumors and the systemic immune response within the host.

2025-08-31 | GSE295942 | GEO

Multimodal chromatin profiling using nanobody-based single-cell CUT&Tag

Project description:Probing epigenomic marks such as histone modifications at a single cell level in thousands of cells has been recently enabled by technologies such as scCUT&Tag. Here we developed a multimodal and optimized iteration of scCUT&Tag called nano-CT (for nano-CUT&Tag) that allows simultaneous probing of three epigenomic modalities at single-cell resolution, using nanobody-Tn5 fusion proteins. nano-CT is compatible with starting materials as low as 25 000 cells and has significantly higher resolution than scCUT&Tag, with a 16-fold increase in the number of fragments per cells. We used nano-CT to simultaneously profile chromatin accessibility, H3K27ac and H3K27me3 in a complex tissue - juvenile mouse brain. The obtained multimodal dataset allowed for discrimination of more cell types/states that scCUT&Tag, and inference of chromatin velocity between ATAC and H3K27ac in the oligodendrocyte (OL) lineage. In addition, we used nano-CT to deconvolute H3K27me3 repressive states and infer two sequential waves of H3K27me3 repression at distinct gene modules during OL lineage progression. Thus, given its high resolution, versatility, and multimodal features, nano-CT allows unique insights in epigenetic landscapes in different biological systems at single cell level.

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Early gene expression changes in peripheral blood leukocytes with rush immunotherapy

Project description:Peripheral blood mononuclear cells (PBMC) were collected from ficoll gradients of whole blood and immediately processed for total RNA and stored at -80oC until use. Blood was from allergic patients at different timepoints pre or post immunotherapy (RIT). Gene expression was compared for the different timepoints. Blood samples were collected from allergic patients before or after rush immunotherapy (RIT), total RNA was prepared and gene expression assessed by Illumina. Samples were collected pre-rush or at 1 week, 7 weeks, 4 months (and for one patient 5 months) after beginning rush immunotherapy. Blood was taken at each timepoint prior to the patient receiving immunotherapy at each timepoint.

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Driver mutation landscape of acute myeloid leukemia provides insights for neoantigen-based immunotherapy [scRNA-seq]

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Multimodal immune profiling to determine mechanisms of COVID-19 clinical trajectory in Uganda

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scRNAseq reveals mechanisms of Merkel cell carcinoma acquired immunotherapy resistance [1]

Project description:scRNAseq reveals mechanisms of Merkel cell carcinoma acquired immunotherapy resistance [1]

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scRNAseq reveals mechanisms of Merkel cell carcinoma acquired immunotherapy resistance [2]

Project description:scRNAseq reveals mechanisms of Merkel cell carcinoma acquired immunotherapy resistance [2]

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scRNAseq reveals mechanisms of Merkel cell carcinoma acquired immunotherapy resistance [1]

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