肿瘤细胞治疗研究
英文原题：Apheresis CD8(+)CCR7(+)CD45RA(-) T-Cells as a Novel Biomarker Associated with CAR T-Cell Kinetics and Clinical Outcome.
我们的数据提示，单采样本中高频率的 CD8⁺ T CM 细胞可能是一种有前景的治疗前生物标志物，与接受 axi-cel 治疗的 r/r LBCL 患者中 CAR-T 强扩增和更优的临床结局相关。
嵌合抗原受体（CAR）T细胞疗法已革新复发或难治性（r/r）弥漫性大B细胞淋巴瘤（DLBCL）的治疗；然而，仍有相当比例患者无法获得持久应答，凸显了对可靠预测性生物标志物的需求。我们分析了23例接受axicabtagene ciloleucel（axi-cel）治疗的r/r大B细胞淋巴瘤（LBCL）患者单采样本中的T淋巴细胞亚群，以鉴定与CAR-T细胞动力学和临床结局相关的治疗前细胞标志物。采用多参数流式细胞术对新鲜单采样本中的T细胞进行免疫表型分析，并监测循环CAR-T细胞。CAR-T细胞计数中位峰值为45.2个/mL。CAR-T强扩增者（峰值≥45.2个/mL）单采样本中的CD4⁺（P=0.011）和CD8⁺（P=0.023）中央记忆T细胞（TCM；CCR7⁺ CD45RA⁻）水平均较高，CD8⁺ CD38⁺ T细胞比例则较低。单采样本中CD8⁺ TCM比例>4.3%可预测CAR-T强扩增（AUC=0.80；P=0.023）；与CD8⁺ TCM低于该阈值者相比，此类患者无进展生存期更长（P=0.04）。我们的数据提示，单采样本中较高比例CD8⁺ TCM可能是治疗前有前景的生物标志物，可预测r/r LBCL患者接受axi-cel后CAR-T细胞强扩增及临床结局改善。
Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL); however, a significant proportion of patients fail to achieve a durable response, underscoring the need for reliable predictive biomarkers. We characterize T-lymphocyte subpopulations in apheresis samples from 23 r/r large B-cell lymphoma (LBCL) patients who received axicabtagene ciloleucel (axi-cel) to identify pre-treatment cell biomarkers associated with CAR T-cell kinetics and clinical outcomes. Immunophenotyping of T-cells within fresh apheresis samples and monitoring of circulating CAR T-cells were performed by multiparametric flow cytometry. The median peak CAR T-cell count was 45.2 CAR T-cells/mL. Strong CAR-T expanders ( 45.2 CAR T-cells/mL) exhibited higher values of both CD4 + ( p = 0.011) and CD8 + ( p = 0.023) central memory T-cells (T CM ; CCR7 + CD45RA - ), as well as lower proportions of CD8 + CD38 + T-cells in apheresis samples. In apheresis, a cut-off value of >4.3% of CD8 + T CM predicted strong CAR-T expansion (AUC: 0.80; p = 0.023) and superior progression-free survival ( p = 0.04) compared with patients who had CD8 + T CM below the cut-off. Our data suggest that high frequencies of CD8 + T CM cells in apheresis samples may represent a promising pre-treatment biomarker associated with strong CAR-T expansion and superior clinical outcome in r/r LBCL patients following axi-cel.
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