Publications by authors named "M J L Ligtenberg"
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. About 10% of affected individuals have an inherited component. Deleterious germline variants increase the lifetime risk for PDAC and are often associated with an elevated risk for extra-pancreatic malignancies.
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- The study explores how the PD-1 immune checkpoint protein is regulated on CD8 T cells, aiming to find ways to lower its abundance without hindering T cell activation, which is crucial for effective cancer therapy.
- Researchers conducted a CRISPR-Cas9 screen on murine CD8 T cells to identify genes impacting PD-1 levels, discovering that inhibiting the TMED protein family, especially TMED10, could reduce PD-1 on the cell surface and enhance T cell function.
- The findings highlight a new regulatory mechanism for PD-1 and suggest that targeting TMED could be a promising therapeutic strategy to improve T cell responses in cancer treatment, as indicated by correlations in mouse models and patient survival data.
Article Synopsis
- This study investigates the effectiveness and safety of a combination therapy using immune checkpoint inhibitors (ICIs) for certain subgroups of metastatic castration-resistant prostate cancer (mCRPC) patients who show an immunogenic profile.
- The trial involved 69 patients with specific genetic markers and assessed the disease control rate after treatment, aiming to exceed 22%.
- Results showed that 38% of patients achieved disease control beyond 6 months, with the highest success in patients with mismatch repair deficiency, but treatment led to significant side effects in some cases, with 20% permanently discontinuing therapy.
Background: Individuals with germline pathogenic variants in BRCA1 or BRCA2 are at a high risk of breast and ovarian carcinomas with BRCA1/2 deficiency and homologous recombination deficiency that can be detected by analysis of genome-wide genomic instability features such as large-scale state transitions, telomeric allelic imbalances, and genomic loss of heterozygosity. Malignancies with homologous recombination deficiency are more sensitive to platinum-based therapies and poly(ADP-ribose) polymerase inhibitors. We investigated the fraction of non-breast or ovarian malignancies that have BRCA1/2 deficiency and genomic instability features.
View Article and Find Full Text PDFMismatch repair (MMR)-deficient cancer evolves through the stepwise erosion of coding homopolymers in target genes. Curiously, the MMR genes MutS homolog 6 (MSH6) and MutS homolog 3 (MSH3) also contain coding homopolymers, and these are frequent mutational targets in MMR-deficient cancers. The impact of incremental MMR mutations on MMR-deficient cancer evolution is unknown.
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