CD4 T cell surface architecture is associated with response to anti-PD-1 therapy in non-small cell lung cancer

In pretreatment peripheral blood mononuclear cells from 62 advanced non-small cell lung cancer patients, CD4 T-cell surface protein organization is linked to anti-PD-1 response, with a CD5-containing domain predicting poor outcome.

• Why it matters: Anti-PD-1 responses in advanced NSCLC vary widely, and existing immune profiling often misses how proteins are spatially arranged on cell surfaces.
• What they did: Using the Proximity Network Assay, the study simultaneously measured cell frequencies, protein abundance, and protein organization in pretreatment samples, then applied machine learning to predict response from CD4 T-cell features.
• The result: Responders showed higher adhesion-associated protein expression and remodeling of a CD5-containing membrane domain; increased colocalization in that domain was associated with poor clinical outcome and reduced survival, and organization predicted response better than abundance alone.

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