肿瘤细胞治疗研究
英文原题：Tumor CD19 Expression Determines Distinct Clinical Outcomes After CD19 CAR T-Cell Therapy in Large B-Cell Lymphoma.
我们在一个 LBCL 队列（n=301）中，通过流式细胞术（FC）、免疫组化和 RNA 测序进行集中定量评估，对肿瘤 CD19 水平开展了整合分析。
对于大 B 细胞淋巴瘤（LBCL），较低的 CD19 表达是否会影响 CD19 CAR-T 治疗结局，仍不明确。研究人员在一组 LBCL 患者（n=301）中，整合流式细胞术（FC）、免疫组织化学及 RNA 测序，对肿瘤 CD19 水平进行集中定量分析。治疗前 FC 检测的 CD19 水平与接受 axicabtagene ciloleucel 或 lisocabtagene maraleucel 后的 1 年无进展生存率相关：CD19 低、中、高表达组分别为 16%、53% 和 64%（p=0.005）。CAR-T 复发后，CD19 低表达肿瘤比例由 17% 升至 35%。免疫组织化学与 RNA 测序也观察到一致的关联。转录组分析显示，较低 CD19 表达与炎症通路相关；这一发现经外部 LBCL 队列（n=1,017）验证。治疗前和治疗后肿瘤中分别有 8% 和 11% 检出 CD19 基因座遗传缺失（p=0.82），未发现 CD19 编码突变。总体而言，CD19 表达是影响 CAR-T 治疗结局的重要临床因素，支持通过定量检测改善风险分层。
It remains uncertain whether lower CD19 expression is clinically relevant for outcomes of CD19 CAR-T therapy of large B-cell lymphoma (LBCL). We conducted an integrative analysis of tumor CD19 levels with centralized quantitative assessment by flow cytometry (FC), immunohistochemistry and RNA-sequencing in a LBCL cohort (n=301). Pre-treatment CD19 by FC correlated with 1-year progression-free survival following axicabtagene ciloleucel or lisocabtagene maraleucel (16%, 53% and 64% for CD19low, CD19intermediate and CD19high, respectively; p=0.005). After CAR-T relapse, proportion of CD19low tumors increased (from 17% to 35%). Concordant associations were observed by immunohistochemistry and RNA-sequencing. Transcriptomic profiling linked lower CD19 to inflammatory pathways, validated in an external LBCL cohort (n=1,017). Genetic loss of the CD19 locus was observed in 8% of pre-CAR-T and 11% of post-CAR-T tumors (p=0.82), while no CD19 coding mutations were identified. Overall, CD19 expression is a clinically meaningful determinant of CAR-T outcomes, supporting quantitative assessment to improve risk stratification.
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