Objective Analysis and Clinical Significance of the Spatial Tumor-Infiltrating Lymphocyte Patterns in Non-Small Cell...

Area of Science:

• Oncology
• Immunology
• Computational Pathology

Background:

• Spatial arrangement of tumor-infiltrating lymphocytes (TILs) is crucial for understanding immune evasion and predicting immunotherapy response.
• Current pathology-based approaches for defining TIL patterns are subjective and lack clear definitions, limiting data interpretation.

Purpose of the Study:

• To investigate the association between spatial TIL patterns and immunotherapy outcomes in non-small cell lung cancer (NSCLC).
• To compare qualitative pathologist-based assessment with an objective, quantitative method for analyzing TIL spatial distribution.

Main Methods:

• Multiplexed immunofluorescence was used to analyze TIL subsets in NSCLC patient samples treated with immune checkpoint inhibitors (ICI).
• Spatial TIL patterns were assessed qualitatively by pathologists and quantitatively by analyzing TIL density ratios in tumor and stromal compartments.
• Associations between spatial patterns and clinical outcomes were evaluated for various TIL markers.

Main Results:

• Qualitative assessment of CD8+ TIL patterns showed limitations, including broad phenotypic spectrums and weak outcome associations.
• An objective classification method identified at least three NSCLC subgroups, partially overlapping with visually defined patterns.
• An "immune excluded-like" subgroup exhibited significantly worse outcomes, suggesting reduced ICI sensitivity, requiring validation.

Conclusions:

• Qualitative spatial TIL pattern evaluation presents significant challenges.
• A novel, objective strategy for spatial TIL analysis was developed, demonstrating strong potential as a biomarker for predicting immunotherapy response in NSCLC.