Publications by authors named "S Charmsaz"
Background And Aims: Isocitrate dehydrogenase 1 ( IDH1 )-mutant cholangiocarcinoma (CCA) is a highly lethal subtype of hepatobiliary cancer that is often resistant to immune checkpoint inhibitor therapies. We evaluated the effects of IDH1 mutations in CCA cells on the tumor immune microenvironment and identified opportunities for therapeutic intervention.
Approach And Results: Analysis of 2606 human CCA tumors using deconvolution of RNA-sequencing data identified decreased CD8+ T cell and increased M2-like tumor-associated macrophage (TAM) infiltration in IDH1 -mutant compared to IDH1 wild-type tumors.
Article Synopsis
- * In a Phase II clinical trial, 27 patients received entinostat followed by nivolumab, resulting in an objective response rate of 11% and a median response duration of over 10 months, although the primary endpoint for overall effectiveness was not reached.
- * The combination treatment led to significant immune profile changes, including increased dendritic cell activity and enhanced inflammatory response, suggesting potential for improving treatment strategies in PDA despite
Article Synopsis
- Immune-related adverse events (irAEs) pose significant risks for patients receiving immune checkpoint inhibitors (ICIs), highlighting the need to identify patients at higher risk and develop strategies to manage these complications.
- An observational study involving 111 patients found that 40.5% experienced symptomatic irAEs, with higher rates linked to combination ICI therapy and pre-existing autoimmune disorders.
- Early increases in specific cytokines and T helper cell populations were associated with developing severe irAEs, indicating potential biomarkers for monitoring and targeting therapeutic interventions.
Article Synopsis
- Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer that resists immunotherapy, largely due to an immunosuppressive environment created by myeloid cells.
- A combination of the PDE5 inhibitor tadalafil with a specific vaccine and immune checkpoint inhibitors shows promise in enhancing the immune response against PDAC, even in cases previously deemed immune-resistant.
- Tadalafil helps reprogram myeloid cells to reduce their suppression of T cells, leading to improved T cell activation and pro-inflammatory signaling, which boosts anti-tumor effects.
Article Synopsis
- Pancreatic cancer is more common in older people and tends to have a worse prognosis for them due to various factors in the tumor microenvironment.
- Research focused on how aged pancreatic fibroblasts, which influence cancer progression, secrete more growth/differentiation factor 15 (GDF-15) compared to younger fibroblasts.
- GDF-15 promotes tumor growth by activating the AKT signaling pathway, indicating that age-related changes in the pancreatic microenvironment contribute to cancer progression and could lead to new treatment strategies.