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Stimulation of oncogene-specific tumor infiltrating T-cells through combined vaccine and alpha-PD1 enable sustained anti-tumor responses against established HER2 breast cancer (BC) [scRNA-Seq]

ABSTRACT: Stimulation of oncogene-specific tumor infiltrating T-cells through combined vaccine and alpha-PD1 enable sustained anti-tumor responses against established HER2 breast cancer (BC) [scRNA-Seq]

PROVIDER: PRJNA624354 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11538400.fastq.gz	Fastqsanger.gz
	SRR11538401.fastq.gz	Fastqsanger.gz
	SRR11538402.fastq.gz	Fastqsanger.gz
	SRR11538403.fastq.gz	Fastqsanger.gz
	SRR11538404.fastq.gz	Fastqsanger.gz

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Stimulation of oncogene-specific tumor infiltrating T-cells through combined vaccine and alpha-PD1 enable sustained anti-tumor responses against established HER2 breast cancer (BC)

Project description:Stimulation of oncogene-specific tumor infiltrating T-cells through combined vaccine and alpha-PD1 enable sustained anti-tumor responses against established HER2 breast cancer (BC)

| PRJNA624350 | ENA

Stimulation of oncogene-specific tumor infiltrating T-cells through combined vaccine and alpha-PD1 enable sustained anti-tumor responses against established HER2 breast cancer (BC) [WXS]

Project description:This study demonstrates two fundamental tenets of immunotherapy: vaccines targeting any tumor antigen will not be as effective as those targeting true oncogenic drivers and neither the stimulation of tumor-specific T-cells nor the blockade of a key immune checkpoint is enough to overcome the layers of immune suppression by itself. It provides single cell genetic evidence that vaccination alone generates a population of CD8 T-cells incapable of long-term tumor control due to the activation of numerous immune dysfunction pathways within the tumor. These promising studies have led to the initiation of a Phase II clinical trial testing a novel HER2 vaccine in combination with Pembrolizumab (NCT03632941) to determine if this combination can elicit effective anti-tumor immunity while minimizing off-target immune responses in patients with advanced HER2+ BC.

2020-04-11 | GSE148478 | GEO

Stimulation of oncogene-specific tumor infiltrating T-cells through combined vaccine and alpha-PD1 enable sustained anti-tumor responses against established HER2 breast cancer (BC) [scRNA-Seq]

2020-04-11 | GSE148480 | GEO

Stimulation of oncogene-specific tumor infiltrating T-cells through combined vaccine and alpha-PD1 enable sustained anti-tumor responses against established HER2 breast cancer (BC) [RNA-Seq]

2020-04-11 | GSE148477 | GEO

Stimulation of oncogene-specific tumor infiltrating T-cells through combined vaccine and alpha-PD1 enable sustained anti-tumor responses against established HER2 breast cancer (BC) [WXS]

| PRJNA624344 | ENA

Stimulation of oncogene-specific tumor infiltrating T-cells through combined vaccine and alpha-PD1 enable sustained anti-tumor responses against established HER2 breast cancer (BC) [RNA-Seq]

| PRJNA624342 | ENA

Stimulation of oncogene-specific tumor infiltrating T-cells through combined vaccine and alpha-PD1 enable sustained anti-tumor responses against established HER2 breast cancer (BC)

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-04-11 | GSE148482 | GEO

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

Project description:We report the gene expression profiles of FACS-sorted PD1-high, PD1-intermediate, and PD1-negative tumor-infiltrating CD8 T cells in hepatocellular carcinoma.

2018-11-13 | GSE111389 | GEO

Therapy of Established Tumors with Rationally Designed Multiple Agents Targeting Diverse Immune-Tumor Interactions: Engage, Expand, Enable

Project description:Immunotherapy of immunologically cold solid tumors may require multiple agents to (a) engage immune effector cells, (b) expand effector populations and activities, and (c) enable immune response in the tumor microenvironment (TME). To target these distinct phenomena, we strategically chose five clinical-stage immuno-oncology agents, namely, (a) a tumor antigen-targeting adenovirus-based vaccine (Ad-CEA) and an IL-15 superagonist (N-803) to activate tumor specific T cells, (b) OX40 and GITR agonists to expand and enhance the activated effector populations, and (c) an IDO inhibitor (IDOi) to enable effector cell activity in the TME. Flow cytometry, TCR sequencing, and RNAseq analyses showed that in the CEA-transgenic murine colon carcinoma (MC38-CEA) tumor model, Ad-CEA + N-803 combination therapy resulted in immune-mediated anti-tumor effects and promoted the expression of costimulatory molecules on immune subsets, OX40 and GITR, and the inhibitory molecule IDO. Treatment with Ad-CEA + N-803 + OX40 + GITR + IDOi, termed the pentatherapy regimen, resulted in the greatest inhibition of tumor growth and protection from tumor rechallenge without toxicity. Monotherapy with any of the agents had little to no anti-tumor activity, while combining two, three, or four agents had minimal anti-tumor effects. Immune analyses demonstrated that the pentatherapy combination induced CD4+ and CD8+ T cell activity in the periphery and tumor and anti-tumor activity associated with decreased Treg immunosuppression in the TME. The pentatherapy combination also inhibited tumor growth and metastatic formation in 4T1 and LL2-CEA murine tumor models. Significance: This study provides the rationale for the combination of multi-modal immunotherapy agents to engage, enhance, and enable adaptive anti-tumor immunity.

2021-02-10 | GSE162799 | GEO

miRNA expression between CD4+PD1+ and CD4+PD1- T cells

Project description:Recent success in cancer immunotherapy has come from the blockade of inhibitory receptors on T cells, such as programmed cell death-1, which can induce a state of T cell exhaustion upon constant antigen stimulation. Understanding miRNA regulation of PD1 can be useful to discover miRNAs for use in therapy or as prognostic markers in various diseases including cancer, autoimmunity and transplantation. We used microarrays to discover global miRNA expression changes upon PD1 upregulation and identified miRNAs that are both up- and down-regulated. B16F10 cells were injected subcutaneously into C57BL/6 mice and 16 days later CD4+PD1+ and CD4+PD1- were sorted from the lymph nodes and spleen for RNA extraction and hybridization on Affymetrix miRNA array.

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