Cellular interactions in the sentinel lymph node predict melanoma recurrence

Area of Science:

• Immunology
• Oncology
• Spatial Biology

Background:

• Melanoma outcomes have improved, yet recurrence persists, especially in later stages.
• The sentinel lymph node (SLN) immune microenvironment, including CD8 T cells and regulatory T cells (Tregs), is altered, but its spatial organization is poorly understood.

Purpose of the Study:

• To investigate the spatial organization of immune cells within melanoma SLNs.
• To identify spatial immune cell interaction patterns associated with melanoma patient outcomes and disease progression.

Main Methods:

• Spatial proteomic profiling of Stage I and II melanoma SLNs using multiplexed immunofluorescence imaging.
• Deep learning for cell segmentation and clustering, identifying 33 immune and tumor cell subsets.
• Effect Size Interaction mapping (ESI-map) to analyze nearest-neighbor cell interactions.

Main Results:

• A foundational spatial map of the melanoma SLN was created, showing distinct immune cell positioning.
• Rewiring of cell-cell interaction pairs was observed across disease progression, particularly involving exhausted TOX+ CD8 T cells.
• Stage II patients with recurrence showed enriched interactions between Tregs and TOX+ CD8 T cells, correlating with reduced cytotoxic markers.

Conclusions:

• Specific spatial interactions between Tregs and exhausted CD8 T cells in the SLN serve as a novel immune signature for predicting melanoma outcomes.
• Understanding the spatial immune microenvironment is crucial for deciphering melanoma progression and recurrence patterns.