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Fluidigm single-cell RNA-seq analysis for gene signatures associated with T-cell persistence

ABSTRACT: A patient (4095) with metastatic colorectal cancer was treated with polyclonal tumor infiltrating lymphocytes (TILs) targeting the KRAS(G12D) hotspot mutation. Three dominant clonotypes specifically recognizing KRAS(G12D) epitopes were identified, but we found that only two clonotypes persisted 40 days after TIL treatment. Because of these findings, in this study, we performed single-cell RNA-seq analysis for the TILs isolated from this patient. This single-cell dataset is generated using a Fluidigm C1 system, followed by a Illumina HiSeq2500 sequencer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE136610 | GEO | 2020/08/28

REPOSITORIES: GEO

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Single-cell transcriptome analysis reveals gene signatures associated with T-cell persistence following adoptive cell therapy

Project description:A patient (4095) with metastatic colorectal cancer was treated with polyclonal tumor infiltrating lymphocytes (TILs) targeting the KRAS(G12D) hotspot mutation. Three dominant clonotypes specifically recognizing KRAS(G12D) epitopes were identified, but we found that only two clonotypes persisted 40 days after TIL treatment. Because of these findings, in this study, we utilized a 10X system to perform single-cell TCR/transcriptome analysis for the TILs isolated from this patient, together with 4 additional TILs isolated from 4 patients (4007, 4069, 4071, 4081) treated within 5-month window. In addition, we performed single-cell TCR/transcriptome analysis on Patient 4095's peripheral blood lymphocytes (PBL) day 12 or day 40 after TIL treatment. We also utilized a low-throughput Fluidigm C1 system to perform single-cell RNA-Seq on TIL4095. Please use accession number GSE136610 to find the dataset.

2019-09-10 | GSE136394 | GEO

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2023-12-29 | E-MTAB-12910 | biostudies-arrayexpress

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2021-07-01 | E-MTAB-10681 | biostudies-arrayexpress

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Project description:Oncogenic mutations in tumor cells regulate signaling both within tumor cells and heterotypic stromal cells. However, whether oncogenes regulate tumor cell signaling via stromal cells is poorly understood. Here we show that oncogenic KRAS (KRAS-G12D) uniquely regulates tumor cell signaling via stromal cells. By combining cell-specific proteome labeling with phosphoproteomic multiplexing we conducted a multivariate analysis of heterocellular KRAS-G12D signaling in Pancreatic Ductal Adenocarcinoma (PDA) cells. By engaging heterotypic fibroblasts, KRAS-G12D drives unique reciprocal signaling in tumor cells to employ additional kinases and double the number of regulated signaling nodes from cell-autonomous KRAS-G12D. Heterocellular signaling produces a distinct tumor cell phosphoproteome, total proteome, and increase mitochondria capacity via an IGF1R/AXL-AKT axis. Reciprocal KRAS-G12D phenotypes require a heterocellular context and are unreachable by cell-autonomous KRAS-G12D alone. These results demonstrate oncogene signaling should be viewed as a heterocellular process and our existing homocellular perspective underrepresents the extent of oncogene signaling in cancer.

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Project description:Purpose: Transcriptome profiling (RNA-seq) was used to compare the expression differences between T in PBMC and TILs Methods:Paired TILs and T in PBMC cells were sorted from fresh patient blood and tumor samples. Then the mRNA were sequeced using xTen platform. The sequence reads that passed quality filters were analyzed. Results: by extract mRNA from tumor infiltrated T cells from ovarian cancer patient sample and T cells from patient bllod samples, we compared the different expressed genes from TIL and T in blood. Hierarchical clustering of differentially expressed genes uncovered several as yet uncharacterized genes that may contribute to T cell exhausetion. Conclusions: We conclude that T in PBMC and TILs share different transcriptome characterization.

2022-12-18 | GSE157936 | GEO

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