PBMCs Bellini TNBC anti-PD1 monotherapy

Immune checkpoint blockade (ICB) combined with chemotherapy (CT) has improved outcome in high-risk early-stage triple-negative breast cancer (TNBC); yet it is unclear which patients benefit from the addition of ICB beyond chemotherapy alone. We profiled 67 serial tumor and 175 blood samples obtained before and during anti-PD1 treatment across 3 breast cancer trials using single-cell transcriptomic and T cell receptor (TCR) sequencing. Early intratumoral T cell expansion emerged as a consistent hallmark of clinical benefit. This expansion was reflected in increased TCR sharing between tumor and blood after treatment initiation, with shared blood T cells displaying immune-activated programs and their tumor counterparts enriched for expanding clonotypes, suggesting blood-to-tumor trafficking of activated T cells. In TNBC treated with anti-PD1+CT, T cell expansion distinguished an immune-driven response from a chemotherapy-dominant route to pathological complete response (pCR). To enable baseline patient stratification, we derived a 15-gene tumor signature predictive of T cell expansion, which associated with response in independent breast cancer cohorts and with improved survival across ICB-treated cancer types. Our data establish T cell expansion as an early marker of sustained ICB response and could allow stratification of patients likely to benefit from the addition of ICB to chemotherapy.

• Type: Transcriptome Analysis
• Archive: European Genome-phenome Archive (EGA)