Integrated Single-Cell and Spatial Analysis Reveals Context-Dependent Myeloid-T Cell Interactions in Response to...

Area of Science:

• Immunology
• Oncology
• Genomics

Background:

• Head and neck squamous cell carcinoma (HNSCC) is a significant global health challenge.
• Immune checkpoint blockade (ICB) has revolutionized cancer treatment but response varies.
• Tumor-infiltrating immune cells and their interactions are critical for ICB efficacy.

Purpose of the Study:

• To systematically evaluate cell-cell interactions among tumor-infiltrating immune cells in HNSCC patients treated with ICB.
• To identify spatial and single-cell omics signatures associated with ICB response.
• To uncover novel ligand-receptor interactions and cellular neighborhoods influencing treatment outcomes.

Main Methods:

• Integrated analysis of Visium spot-based spatial transcriptomics and CosMx SMI single-cell spatial omics.
• Utilized a 64-plex protein panel and a 1000-gene RNA panel, including 435 ligands and receptors.
• Bioinformatics approaches to identify co-localizing cell types and ligand-receptor interactions.

Main Results:

• Identified spatial and cell-type specific differences in myeloid and T cell interactions between ICB responders and non-responders.
• Defined cellular neighborhoods and sources of CXCL9/10-CXCR3 interactions, crucial in responders.
• Highlighted other potential ICB response markers like CXCL16-CXCR6 and CCL4/5-CCR5.

Conclusions:

• Provided a resource for analyzing spatial ligand-receptor interactions in the context of ICB response.
• Emphasized the context specificity of ICB response biomarkers and targets.
• Recommended considering spatial context in future mechanistic studies of ICB biomarkers.