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.
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.
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.
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.
Project description:Analysis of peripheral circulating mRNA expression levels in patients undergoing neoadjuvant chemoradiation for esophageal squamous cell carcinoma. The hypothesis test was that chemoradiation alters the circulating mRNA expression profiles and the profiling is predictive of pathological response. Results provide information on the response of circulating mRNAs to chemoradiation and identify novel biomarkers or targets in esophageal squamous cell carcinoma. Total RNA obtained from peripheral whole blood before and after neoadjuvant chemoradiation in patients with esophageal squamous cell carcinoma. 21 patients with 42 samples were analyzed. The expression profiles from pathological complete responders were compared to non-complete responders.
