Single-cell and spatial transcriptomics reveal SPP1-CD44 signaling drives primary resistance to immune checkpoint inhibitors in RCC.

ABSTRACT:

Background

Immune checkpoint inhibitors (ICIs) are a cornerstone therapy for advanced renal cell carcinoma (RCC). However, significant rates of primary resistance hinder their efficacy, and the underlying mechanisms remain poorly understood. This study aims to unravel the tumor-immune interactions and signaling pathways driving primary resistance to ICIs in RCC.

Methods

We integrated single-cell RNA sequencing, spatial transcriptomics, and clinical sample analysis to investigate the tumor microenvironment and intercellular signaling. Advanced computational methods, including cell-cell communication networks, pseudotime trajectories, and gene set enrichment analysis (GSEA), were employed to uncover the underlying resistance mechanisms.

Results

Compared to the sensitive

SUBMITTER: Zhang J 

PROVIDER: S-EPMC11687132 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature