Publications by authors named "Alexia Alfaro"
Chronic myelomonocytic leukemia (CMML) is a severe myeloid malignancy with limited therapeutic options. Single-cell analysis of clonal architecture demonstrates early clonal dominance with few residual WT hematopoietic stem cells. Circulating myeloid cells of the leukemic clone and the cytokines they produce generate a deleterious inflammatory climate.
View Article and Find Full Text PDFRadiotherapy (RT) triggers an immune response that contributes to anti-tumor effects. Induction of interferon beta (IFN-β) is a key event in this immunogenicity of RT. We have previously shown that TRIM33, a chromatin reader, restrains IFN-β expression in Toll-like receptor-activated myeloid cells.
View Article and Find Full Text PDFArticle Synopsis
- Recent clinical trials of new immune checkpoint protein-targeted antibodies failed to show significant results, primarily because patients weren't screened for target expression prior to treatment.* -
- The study utilized advanced methods like flow cytometry and single-cell RNA sequencing to analyze immune checkpoint expression on T-cells from various primary tumors, revealing extensive variability among patients.* -
- Results indicated that while CD4FoxP3 T-cells co-expressed both stimulatory and inhibitory checkpoints, the expression levels in CD8 T-cells were generally lower, suggesting a need for better-targeted therapies in future cancer immunotherapy trials.*
The mechanisms of action of and resistance to trastuzumab deruxtecan (T-DXd), an anti-HER2-drug conjugate for breast cancer treatment, remain unclear. The phase 2 DAISY trial evaluated the efficacy of T-DXd in patients with HER2-overexpressing (n = 72, cohort 1), HER2-low (n = 74, cohort 2) and HER2 non-expressing (n = 40, cohort 3) metastatic breast cancer. In the full analysis set population (n = 177), the confirmed objective response rate (primary endpoint) was 70.
View Article and Find Full Text PDFHeterozygous mutation targeting proline 95 in Serine/Arginine-rich Splicing Factor 2 (SRSF2) is associated with V617F mutation in Janus Activated Kinase 2 (JAK2) in some myeloproliferative neoplasms (MPNs), most commonly primary myelofibrosis. To explore the interaction of Srsf2 with Jak2, we generated Cre-inducible knock-in mice expressing these mutants under control of the stem cell leukemia (Scl) gene promoter. In transplantation experiments, Srsf2 unexpectedly delayed myelofibrosis induced by Jak2 and decreased TGFβ1 serum level.
View Article and Find Full Text PDFPurpose: Severe pneumonia and acute respiratory distress syndrome (ARDS) have been described in patients with severe coronavirus disease 2019 (COVID-19). Recently, early clinical data reported the feasibility of low doses of radiation therapy (RT) in the treatment of ARDS in patients with severe COVID-19. However, the involved mechanisms remained unknown.
View Article and Find Full Text PDFArticle Synopsis
- Blood myeloid cells show dysregulation in COVID-19, with changes in monocyte and neutrophil populations linked to disease severity.
- In severe cases, there's a notable decrease in non-classical CD14CD16 monocytes and an accumulation of HLA-DR classical monocytes, along with high levels of calprotectin.
- The findings suggest that measuring calprotectin levels and non-classical monocyte frequencies could help predict which COVID-19 patients are at higher risk for severe illness, indicating a need for further study.
Background And Objectives: In head and neck surgery, intraoperative and postoperative evaluation of tumor margins is achieved by histopathological assessment, which is a multistep process. Intraoperative analysis of tumor margins to obtain a preliminary diagnosis is usually carried out on frozen sections. Analysis of frozen sections is challenging due to technical difficulties in processing.
View Article and Find Full Text PDF