Differential Infiltration of Key Immune T-Cell Populations Across Malignancies Varying by Immunogenic Potential and the Likelihood of Response to Immunotherapy.

Solid tumors vary by the immunogenic potential of the tumor microenvironment (TME) and the likelihood of response to immunotherapy. The emerging literature has identified key immune cell populations that significantly impact immune activation or suppression within the TME. This study investigated candidate T-cell populations and their differential infiltration within different tumor types as estimated from mRNA co-expression levels of the corresponding cellular markers.

Tumor-derived CCL2 drives tumor growth and immunosuppression in IDH1- mutant cholangiocarcinoma.

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.

The Functional Transcriptomic Landscape Informs Therapeutic Strategies in Multiple Myeloma.

Several therapeutic agents have been approved for treating multiple myeloma, a cancer of bone marrow-resident plasma cells. Predictive biomarkers for drug response could help guide clinical strategies to optimize outcomes. In this study, we present an integrated functional genomic analysis of tumor samples from patients multiple myeloma that were assessed for their ex vivo drug sensitivity to 37 drugs, clinical variables, cytogenetics, mutational profiles, and transcriptomes.

Multicellular immune ecotypes within solid tumors predict real-world therapeutic benefits with immune checkpoint inhibitors.

Background: Cancer initiation, progression, and immune evasion depend on the tumor microenvironment (TME). Thus, understanding the TME immune architecture is essential for understanding tumor metastasis and therapy response. This study aimed to create an immune cell states (CSs) atlas using bulk RNA-seq data enriched by eco-type analyses to resolve the complex immune architectures in the TME.

The E592K variant of SF3B1 creates unique RNA missplicing and associates with high-risk MDS without ring sideroblasts.

Among the most common genetic alterations in myelodysplastic syndromes (MDS) are mutations in the spliceosome gene SF3B1. Such mutations induce specific RNA missplicing events, directly promote ring sideroblast (RS) formation, and generally associate with a more favorable prognosis. However, not all SF3B1 mutations are the same, and little is known about how distinct hotspots influence disease.