Spatial Transcriptomics of Immune Cell Distribution in Non-Small Cell Lung Cancer Identifies Tertiary Lymphoid...

Area of Science:

• Immunology
• Oncology
• Genomics

Background:

• Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality.
• Single-cell sequencing lacks spatial context for cell interactions.
• Tertiary lymphoid structures (TLS) require spatial immune cell distribution data, and their role in neoadjuvant therapy is unclear.

Purpose of the Study:

• To investigate the spatial distribution and characteristics of immune cells within NSCLC.
• To explore the relationship between TLS and patient response to neoadjuvant therapy (ICI combined with chemotherapy).

Main Methods:

• Spatial transcriptomics and multiplex immunohistochemistry (mIHC) were performed on NSCLC samples.
• TLS status, cell characteristics, density, and area proportion were evaluated.
• Associations between TLS metrics and patient response were analyzed in 66 patients.

Main Results:

• Immune cell heterogeneity was observed, with activated B and T cells inside TLS, and plasma cells/macrophages outside.
• Genes related to antigen-presenting machinery (APM) were upregulated within TLS.
• Mature TLS (mTLS) had a larger area and higher density compared to immature TLS.
• Higher TLS and mTLS density and B-cell density were found in the responder group.

Conclusions:

• Spatial transcriptomics reveals distinct immune cell localization patterns in NSCLC.
• APM genes are highly expressed in TLS, suggesting a role in immune response.
• mTLS, characterized by more B cells, are larger.
• Increased TLS and mTLS density correlate with better response to neoadjuvant therapy, indicating potential anti-tumor function.