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Sequential chemoimmunotherapy in gastric cancer

ABSTRACT: Sequential pembrolizumab cooperates with platinum/5FU to remodel the tumor immune microenvironment in advanced gastric cancer: A phase II sequential chemoimmunotherapy trial

PROVIDER: PRJEB58725 | ENA |

REPOSITORIES: ENA

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Sequential pembrolizumab cooperates with platinum/5FU to remodel the tumor immune microenvironment in advanced gastric cancer: A phase II chemoimmunotherapy trial

Project description:Sequential pembrolizumab cooperates with platinum/5FU to remodel the tumor immune microenvironment in advanced gastric cancer: A phase II chemoimmunotherapy trial

| PRJEB60680 | ENA

Sequential pembrolizumab cooperates with platinum/5FU to remodel the tumor immune microenvironment in advanced gastric cancer: A phase II chemoimmunotherapy trial

Project description:Sequential pembrolizumab cooperates with platinum/5FU to remodel the tumor immune microenvironment in advanced gastric cancer: A phase II chemoimmunotherapy trial

| PRJEB60681 | ENA

Coupling of response biomarkers between tumour and peripheral blood in mesothelioma patients undergoing chemoimmunotherapy

Project description:Platinum-based chemotherapy in combination with anti-PD-L1 antibodies has shown promising results in mesothelioma. However, the immunological mechanisms underlying its efficacy are not well understood and there are no predictive biomarkers of clinical outcomes to guide treatment decisions. Here, we combine time-course RNA sequencing of peripheral blood mononuclear cells with pre-treatment tumour transcriptome data from the 54-patient cohort in the single arm phase II DREAM study. The identified immunological correlates are predictive of response and provide further evidence for the additive nature of the interaction between platinum-based chemotherapy and PD-L1 antibodies. Our study highlights the complex, but predictive interactions between the tumour and immune cells in peripheral blood during the response to chemoimmunotherapy.

2024-10-31 | GSE248514 | GEO

Coupling of response biomarkers between tumour and peripheral blood in patients undergoing chemoimmunotherapy

Project description:Platinum-based chemotherapy in combination with anti-PD-L1 antibodies has shown promising results in mesothelioma. However, the immunological mechanisms underlying its efficacy are not well understood and there are no predictive biomarkers of clinical outcomes to guide treatment decisions. Here, we combine time-course RNA sequencing of peripheral blood mononuclear cells with pre-treatment tumour transcriptome data from the 54-patient cohort in the single arm phase II DREAM study. In peripheral blood, CD8 + T effector memory cells with stem-like properties are more abundant in responders at baseline, 3 weeks, and 6 weeks into therapy. These peripheral blood changes are linked to the transcriptional state of the tumour microenvironment. The identified immunological correlates are predictive of response and provide further evidence for the additive nature of the interaction between platinum-based chemotherapy and PD-L1 antibodies. Our study highlights the complex, but predictive interactions between the tumour and immune cells in peripheral blood during the response to chemoimmunotherapy.

2024-10-31 | GSE252432 | GEO

Coupling of response biomarkers between tumour and peripheral blood in patients undergoing chemoimmunotherapy

Project description:Platinum-based chemotherapy in combination with anti-PD-L1 antibodies has shown promising results in mesothelioma. However, the immunological mechanisms underlying its efficacy are not well understood and there are no predictive biomarkers to guide treatment decisions. Here, we combine time-course RNA sequencing of peripheral blood mononuclear cells with pre-treatment tumour transcriptome data from the 54-patient single arm phase II DREAM study. Single cell RNA-seq and TCR-seq reveal CD8+ T effector memory (TEM) cells with stem-like properties are more abundant in peripheral blood of responders and this population expands upon treatment. These peripheral blood changes are linked to the transcriptional state of the tumour microenvironment. Combining information from both compartments, rather than individually, is most predictive of response. Our study highlights the complex, but predictive interactions between the tumour and immune cells in peripheral blood during the response to chemoimmunotherapy.

2024-10-31 | GSE252990 | GEO

MEK inhibition overcomes chemoimmunotherapy resistance by inducing CXCL10 in cancer cells [LLC1]

Project description:Chemotherapy with anti PD-1/PD-L1 mAb has become the standard of care for patients with metastatic non-small cell lung cancer (NSCLC). Using lung tumor models, where pemetrexed-platinum chemotherapy (PEM/CDDP) remains unable to synergize with immune checkpoint inhibitors (ICI), we linked failure of this treatment with its inability to induce CXCL10 expression and CD8+ T cell recruitment. Using drug screening, we showed that combining a MEK inhibitor (MEKi) with PEM/CDDP triggers CXCL10 secretion by cancer cells and CD8+ T cell recruitment, and restores ICI efficacy. PEM/CDDP plus MEKi promotes optineurin (OPTN)-dependent mitophagy, resulting in CXCL10 production in a mitochondrial DNA and TLR9-dependent manner. TLR9 or autophagy/mitophagy processes genetic inactivation of abort the antitumor efficacy of PEM/CDDP plus MEKi/anti PD-L1 therapy. In human NSCLC, high OPTN, TLR9 and CXCL10 expression is associated with better response to ICI. Our results underline the role of TLR9 and OPTN-dependent mitophagy in enhancing chemoimmunotherapy efficacy.

2021-12-08 | GSE190264 | GEO

MEK inhibition overcomes chemoimmunotherapy resistance by inducing CXCL10 in cancer cells [France4]

2021-12-08 | GSE190266 | GEO

MEK inhibition overcomes chemoimmunotherapy resistance by inducing CXCL10 in cancer cells [France3]

2021-12-08 | GSE190265 | GEO

Coupling of response biomarkers between tumour and peripheral blood in patients undergoing chemoimmunotherapy II

Project description:Platinum-based chemotherapy in combination with anti-PD-L1 antibodies has shown promising results in mesothelioma. However, the immunological mechanisms underlying its efficacy are not well understood and there are no predictive biomarkers to guide treatment decisions. Here, we combine time-course RNA sequencing of peripheral blood mononuclear cells with pre-treatment tumour transcriptome data from the 54-patient single arm phase II DREAM study. Single cell RNA-seq and TCR-seq reveal CD8+ T effector memory (TEM) cells with stem-like properties are more abundant in peripheral blood of responders and this population expands upon treatment. These peripheral blood changes are linked to the transcriptional state of the tumour microenvironment. Combining information from both compartments, rather than individually, is most predictive of response. Our study highlights the complex, but predictive interactions between the tumour and immune cells in peripheral blood during the response to chemoimmunotherapy.

2024-10-31 | GSE253173 | GEO

Sequential azacitidine and carboplatin can prime high-grade serous ovarian cancer to respond to checkpoint inhibitor immunotherapy.

Project description:Platinum chemoresistance results in disease recurrence in patients with high-grade serous ovarian cancer (HGSOC). Recent advances in the treatment of solid tumours using checkpoint inhibitor immunotherapy has not benefited platinum-resistant HGSOC. Epigenetic silencing of genes involved in triggering cell death and apoptosis in HGSOC is known to occur via hypermethylation during development of platinum resistance. DNA methyltransferase (DNMT) inhibitors block methylation from occurring and allow silenced genes to be expressed. In ovarian cancer, DNMT inhibitors alter the epigenome and transcriptome of the tumours, which primarily affected expression of immune reactivation pathways. We aimed to determine the epigenome and transcriptome response to sequential treatment of HGSOC cells with DNMTi followed by standard-of-care carboplatin.

2022-02-02 | GSE169617 | GEO

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