Publications by authors named "W J Lesterhuis"
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 (RNA-seq) of peripheral blood mononuclear cells with pre-treatment tumor transcriptome data from the single-arm, phase 2 DREAM trial (N = 54).
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- Antibodies targeting immune checkpoints like CTLA-4 and PD-1/PD-L1 are used to treat various cancers, often combined with chemotherapy, but the role of other checkpoints like LAG-3 is less understood.
- * Recent studies showed that chemotherapy increases the presence of specific T cells (both CD4 and CD8) expressing LAG-3 in tumors, suggesting a broader effect on immune response.
- * Combining anti-LAG-3 and anti-PD-1 therapies with chemotherapy led to significantly better tumor control than using any of the treatments alone, indicating the importance of how chemotherapy changes immune checkpoint expression in treatment strategies.*
Toll-like receptor (TLR) agonists are being developed as anti-cancer therapeutics due to their potent immunostimulatory properties. However, clinical trials testing TLR agonists as monotherapy have often failed to demonstrate significant improvement over standard of care. We hypothesized that the anti-cancer efficacy of TLR agonist immunotherapy could be improved by combinatorial approaches.
View Article and Find Full Text PDFMany mechanisms underlying an effective immunotherapy-induced antitumour response are transient and critically time dependent. This is equally true for several immunological events in the tumour microenvironment induced by other cancer treatments. Immune checkpoint therapy (ICT) has proven to be very effective in the treatment of some cancers, but unfortunately, with many cancer types, most patients do not experience a benefit.
View Article and Find Full Text PDFTime-critical transcriptional events in the immune microenvironment are important for response to immune checkpoint blockade (ICB), yet these events are difficult to characterise and remain incompletely understood. Here, we present whole tumor RNA sequencing data in the context of treatment with ICB in murine models of AB1 mesothelioma and Renca renal cell cancer. We sequenced 144 bulk RNAseq samples from these two cancer types across 4 time points prior and after treatment with ICB.
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