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

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. Peripheral blood samples were drawn at three timepoints. The first was taken at pretreatment baseline prior to dexamethasone pre-medication (Baseline). The subsequent two samples were taken before the second (C2D1) and third cycles (C3D1) of chemoimmunotherapy treatment. A window of up to 7 days was permitted before timepoint 0 bloods, and a window of up to 3 days before treatment administration was permitted before timepoint 1 and timepoint 2 bloods. ---------------------------- Authors state "raw data were not submitted due to patient privacy concerns".