Duvelisib with docetaxel for patients with anti-PD-1 refractory, recurrent or metastatic head and neck squamous cell carcinoma.

Background: Treatments after anti-PD-1 therapy for patients with recurrent, metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) are limited. Blocking phosphatidylinositol 3-kinase (PI3K) signaling may lead to tumor immunomodulation and enhanced taxane sensitivity. This phase 2 trial evaluated dual, selective PI3Kδ/γ inhibition with docetaxel in patients with anti-PD-1 refractory R/M HNSCC.

Spatial mapping of human hematopoiesis at single-cell resolution reveals aging-associated topographic remodeling.

The spatial anatomy of hematopoiesis in the bone marrow (BM) has been extensively studied in mice and other preclinical models, but technical challenges have precluded a commensurate exploration in humans. Institutional pathology archives contain thousands of paraffinized BM core biopsy tissue specimens, providing a rich resource for studying the intact human BM topography in a variety of physiologic states. Thus, we developed an end-to-end pipeline involving multiparameter whole tissue staining, in situ imaging at single-cell resolution, and artificial intelligence-based digital whole slide image analysis and then applied it to a cohort of disease-free samples to survey alterations in the hematopoietic topography associated with aging.

Analysis of Primary Liquid Chromatography Mass Spectrometry Data by Neural Networks for Plant Samples Classification.

Plant samples are potential sources of physiologically active secondary metabolites and their classification is an extremely important task in traditional medicine and other fields of research. In the production of herbal drugs, different plant parts of the same or related species can serve as adulterants for primary plant material. The use of highly informative and relatively easily accessible tools, such as liquid chromatography and low-resolution mass spectrometry, helps to solve these tasks by means of fingerprint analysis.

Multiregional single-cell proteogenomic analysis of ccRCC reveals cytokine drivers of intratumor spatial heterogeneity.

Intratumor heterogeneity (ITH) represents a major challenge for anticancer therapies. An integrated, multidimensional, multiregional approach dissecting ITH of the clear cell renal cell carcinoma (ccRCC) tumor microenvironment (TME) is employed at the single-cell level with mass cytometry (CyTOF), multiplex immunofluorescence (MxIF), and single-nucleus RNA sequencing (snRNA-seq) and at the bulk level with whole-exome sequencing (WES), RNA-seq, and methylation profiling. Multiregional analyses reveal unexpected conservation of immune composition within each individual patient, with profound differences among patients, presenting patient-specific tumor immune microenvironment signatures despite underlying genetic heterogeneity from clonal evolution.