Single-cell spatial analysis with Xenium reveals anti-tumour responses of CXCL13 + T and CXCL9+ cells after radiotherapy combined with anti-PD-L1 therapy.

Background: The standard treatment for unresectable non-small cell lung cancer (NSCLC) is anti-PD-L1 therapy combined with chemoradiotherapy (anti-PD-L1-CRT). Although some patients achieve complete cancer eradication and cure, more than half of patients retain persistent cancer cells. Our research aimed to unravel the nuanced mechanisms involved in both immune attack and evasion induced by anti-PD-L1-CRT with single cell spatial transcriptome.

Microbiome Landscape and Association with Response to Immune Checkpoint Inhibitors in Advanced Solid Tumors: A SCRUM-Japan MONSTAR-SCREEN Study.

Unlabelled: Although the gut microbiome is associated with cancer development and progression, little is known about the effects of the gut microbiome landscape and the efficacy of immune checkpoint inhibitors (ICI) across cancer types. We investigated the association between the microbiome, clinical features, and ICI efficacy across cancer types in a large nationwide screening project for solid tumors. Among 2,180 patients with advanced solid tumors enrolled in the SCRUM-Japan MONSTAR-SCREEN between October 2019 and September 2021, in the chemotherapy-naïve cohort (n = 817), a high prevalence of oral bacteria was observed in patients using proton pump inhibitors (PPI) and those with upper gastrointestinal cancers, particularly postoperative patients with gastric or pancreatic cancer.

SpatialKNifeY (SKNY): Extending from spatial domain to surrounding area to identify microenvironment features with single-cell spatial omics data.

Single-cell spatial omics analysis requires consideration of biological functions and mechanisms in a microenvironment. However, microenvironment analysis using bioinformatic methods is limited by the need to detect histological morphology and extend it to the surrounding area. In this study, we developed SpatialKNifeY (SKNY), an image-processing-based toolkit that detects spatial domains that potentially reflect histology and extends these domains to the microenvironment.

Mathematical Modeling Predicts Optimal Immune Checkpoint Inhibitor and Radiotherapy Combinations and Timing of Administration.

Radiotherapy (RT) combined with immune checkpoint inhibitor (ICI) therapy has attracted substantial attention due to its potential to improve outcomes for patients with several types of cancer. However, the optimal administration timepoints and drug combinations remain unclear because the mechanisms underlying RT-induced changes in immune checkpoint molecule expression and interaction with their ligand(s) remain unclear. In this study, we demonstrated the dynamics of lymphocyte-mediated molecular interactions in tissue samples from patients with esophageal cancer throughout RT schedules.