Computational immune synapse analysis reveals T-cell interactions in distinct tumor microenvironments

Area of Science:

• Immunology
• Computational Biology
• Oncology

Background:

• The tumor microenvironment (TME) and its cellular interactions significantly impact tumor progression and treatment outcomes.
• Advanced multiplex imaging technologies generate rich TME data, but methods for analyzing cellular interactions are still developing.

Approach:

• Developed multipronged computational immune synapse analysis (CISA) for automated discovery and quantification of T-cell synaptic interactions from multiplex images.
• Validated CISA using human melanoma imaging mass cytometry (IMC) datasets and histocytometry whole slide images.
• Extended CISA to breast cancer IMC data to assess its generalizability.

Key Points:

• CISA accurately detects T-cell:antigen-presenting cell (APC) synapses in melanoma.
• In melanoma, T-cell:macrophage synapse formation correlates with T-cell proliferation.
• CISA-quantified T-cell:B-cell synapses in breast cancer predict improved patient survival.

Conclusions:

• Spatially resolved cell-cell synaptic interactions in the TME hold significant biological and clinical importance.
• CISA provides a robust, versatile method for analyzing synaptic interactions across diverse imaging modalities and cancer types.
• This approach enhances the understanding of immune cell communication within the TME and its implications for cancer therapy.