源自肿瘤微环境的无细胞 RNA 特征预测大 B 细胞淋巴瘤 CAR-T 疗法的结局

Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy can induce durable remissions in patients with large B-cell lymphoma (LBCL), yet outcomes remain variable. Reliable pre-treatment predictors of durable response remain limited, leaving a critical gap in patient management. To address this, we profiled pre-treatment plasma cell-free RNA (cfRNA) from 91 LBCL patients treated with axicabtagene ciloleucel (axi-cel, Yescarta) across three independent cohorts.

We first demonstrated that signatures of "lymph node-like" tumor microenvironments (TMEs), previously identified in tumor biopsies and shown to correlate with favorable outcomes, are specifically elevated in the pre-treatment plasma cfRNA of responders, but not in matched peripheral blood mononuclear cells (PBMCs). These observations indicate that cfRNA captures TME tissue-derived signals not reflected in circulating immune cells.

Next, using unbiased approaches, we identified additional cfRNA signatures associated with one-year clinical outcomes that capture the underlying biological landscape of treatment response. Collectively, these findings support pre-treatment plasma cfRNA as a minimally invasive surrogate of TME state to prospectively inform durable CAR T-cell therapy outcomes and guide risk stratification and TME-modulating adjunct therapies.