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Gene expression profiles of PD1-high, PD1-intermediate, and PD1-negative tumor-infiltrating CD8 T cells in hepatocellular carcinoma

ABSTRACT: Gene expression profiles of PD1-high, PD1-intermediate, and PD1-negative tumor-infiltrating CD8 T cells in hepatocellular carcinoma

PROVIDER: PRJNA436904 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6805260.fastq.gz	Fastqsanger.gz
	SRR6805270.fastq.gz	Fastqsanger.gz
	SRR6805261.fastq.gz	Fastqsanger.gz
	SRR6805271.fastq.gz	Fastqsanger.gz
	SRR6805262.fastq.gz	Fastqsanger.gz

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Gene expression profiles of PD1-high, PD1-intermediate, and PD1-negative tumor-infiltrating CD8 T cells in hepatocellular carcinoma

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Project description:Background: Cancer Immunotherapy with cytokines has demonstrated clinical efficacy but is frequently accompanied with severe adverse events caused by excessive and systemic immune activation. Here, we addressed these challenges by engineering a fusion protein of a single, potency-reduced, IL-15 mutein and an anti-PD1 antibody (αPD1-IL15m). This immunocytokine is designed to deliver PD1-mediated avidity-driven IL-2/15 receptor stimulation preferentially to PD1-positive tumor-infiltrating lymphocytes (TILs) while reducing the natural preference of IL-15 for circulating peripheral NK or T cell Methods: We isolated human lymphocytes from resected hepatocellular carcinoma tissue and cultured these tumor-infiltrating lymphocytes (TILs) in vitro in the presence or absence of an PD1-targeted IL15 mutein, anti-PD1 antibody or IL-15 agonist. After 9 days, CD4+ TILs and CD8+ TILs were sorted by FACS and RNA of 3,000 to 150,000 cells was isolated. Results: The PD1-IL15 fusion cytokine enhanced pro-survival, proliferation and activation pathways in tumor-infiltrating CD4+ and CD8+ cells compared to untreated controls as well as to the combined treatment of single agents (anti-PD1 antibody and IL-15 agonist)

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Gene expression profiles of tumor-infiltrating CD8 T cells in hepatocellular carcinoma

Project description:Gene expression profiles of tumor-infiltrating CD8 T cells in hepatocellular carcinoma

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