Automated prognostic pattern detection shows favourable diffuse pattern of FOXP3(+) Tregs in follicular lymphoma

Area of Science:

• Oncology
• Computational Pathology
• Immunohistochemistry

Background:

• Histopathological prognostication faces challenges with increasing biomarker numbers, potentially overwhelming human pattern recognition.
• Follicular lymphoma (FL) exhibits variable outcomes, influenced by regulatory T cells (Tregs) expressing FOXP3.
• Hypothesised interaction distribution (HID) analysis is a novel automated method for spatial biomarker pattern analysis.

Purpose of the Study:

• To apply HID analysis to tumour-infiltrating lymphocytes in FL to identify prognostic spatial patterns.
• To investigate the association between T cell distribution patterns and patient survival in FL.

Main Methods:

• Utilized a tissue microarray of 40 FL patient samples.
• Performed triplex immunohistochemistry for FOXP3, CD3, and CD69, followed by multispectral imaging.
• Applied HID analysis to correlate spatial T cell patterns with clinical outcomes.

Main Results:

• Increased numbers of CD3(+), FOXP3/CD3(+), and CD69/CD3(+) T cells were associated with favorable prognoses.
• Cross-validated HID analysis identified patient subgroups with significantly different survival rates (35.5 vs. 142 months).
• A diffuse cellular pattern correlated with favorable outcomes, while an aggregated pattern indicated unfavorable outcomes.

Conclusions:

• HID analysis successfully identified prognostic cellular patterns in FL, specifically a diffuse pattern of FOXP3 and CD69 positivity as favorable.
• This unsupervised, automated method is scalable for analyzing multiple biomarkers.
• HID analysis offers a powerful tool for discovering novel prognostic cellular patterns in cancer tissue samples.