Pan-cancer analysis of spatial transcriptomics reveals heterogeneous tumor spatial microenvironment

Area of Science:

• Oncology
• Systems Biology
• Genomics

Background:

• Tumors are complex ecosystems with diverse cell types.
• The tumor spatial microenvironment (TSME) significantly impacts tumor progression.
• Understanding cellular interactions within the TSME is crucial for cancer research.

Purpose of the Study:

• To perform a pan-cancer spatial transcriptomic analysis.
• To identify and characterize local cellular programs (LCPs) and recurrent niches within the TSME.
• To investigate the relationship between niche composition, cellular communication, and clinical outcomes.

Main Methods:

• Spatial transcriptomic analysis of 373 samples across 12 cancer types.
• Identification of 56 LCPs and 13 recurrent niches.
• Ligand-receptor interaction analysis to map cellular communication networks.

Main Results:

• Discovered 56 LCPs and 13 recurrent niches across diverse cancers.
• Revealed niche-specific and shared ligand-receptor interactions driving spatial organization.
• Demonstrated that gene expression in tumor cells and macrophages is location-dependent.
• Associated specific niches with clinical outcomes, including prognosis and immunotherapy response.

Conclusions:

• The TSME is structured into recurrent niches with distinct cellular programs and communication patterns.
• Niche composition significantly influences tumor cell and macrophage gene expression.
• Specific niches correlate with patient prognosis and response to immunotherapy, offering potential therapeutic targets.