Parallel single-cell and bulk transcriptome analyses reveal key features of the gastric tumor microenvironment

Area of Science:

• Oncology
• Immunology
• Genomics

Background:

• The tumor microenvironment (TME) critically impacts cancer treatment outcomes and patient survival.
• Gastric cancer TME cellular composition and function remain incompletely understood.

Purpose of the Study:

• To comprehensively characterize the cellular landscape and transcriptional programs within the gastric cancer TME.
• To identify TME cell types associated with malignant transformation and treatment response.

Main Methods:

• Integrated analysis of bulk and single-cell RNA sequencing from 24 treatment-naïve gastric cancer patients.
• Clustering of over 96,000 non-epithelial cells to define TME cell types.
• Intercellular network reconstruction and survival analysis in an independent cohort.

Main Results:

• Identified 81 distinct TME cell types, with activated fibroblasts and endothelial cells overrepresented in tumors.
• Demonstrated that immunosuppressive myeloid cells and regulatory T cells create a microenvironment associated with poor prognosis and anti-PD1 resistance.
• Discovered that IFNγ-activated T cells and HLA-II expressing macrophages are linked to improved survival and treatment response.

Conclusions:

• The gastric cancer single-cell TME compendium offers a valuable resource for identifying novel biomarkers for patient stratification.
• Elucidates mechanisms underlying gastric cancer progression and provides insights for therapeutic strategies.