Blood：全基因组测序揭示CAR-19 T细胞治疗淋巴瘤失败的潜在复杂基因组特征

2022-08-18 MedSci原创 MedSci原创

肿瘤固有基因组变异是CAR-19 T细胞疗法对大B细胞淋巴瘤疗效和耐药性的复杂相互作用因素的关键

CD19靶向嵌合抗原受体 (CAR-19) T细胞是一种突破性的免疫疗法，已被批准用于治疗大B细胞淋巴瘤。虽然52%-82%的患者对CAR-19治疗有反应，但只有40%左右的患者可获得完全缓解。迄今为止，CAR-19 T细胞治疗失败的潜在机制尚不明确。

已知宿主炎症和肿瘤微环境标记物与CAR-19疗效和耐药性相关，但这些现象背后的肿瘤内在改变仍不明确。CD19突变与耐药性相关，但并不常见，而且大多数复发患者仍保留野生型受体的表达，这提示还有其他基因组机制参与耐药性的产生。

与早期预后相关的临床特征

Michael等研究人员利用全基因组测序的综合分辨率来评估来自49位CAR-19治疗的大B细胞淋巴瘤患者的51份肿瘤样本，发现复杂结构变异、APOBEC突变标记和活性氧物种的基因组损伤的存在可预测CAR-19耐药性的出现。

此外，包含RHOA肿瘤抑制因子的复发性3p21.31染色体缺失在CAR-T细胞治疗失败的患者中显著富集。

有无APOBEC突变的患者经CAR-19治疗后的生存率

预处理降低CD19表达或单等位基因缺失均不影响治疗反应，这表明CAR-19治疗的成功和耐药性与多种机制有关。

综上，该研究表明，肿瘤固有基因组变异是CAR-19 T细胞疗法对大B细胞淋巴瘤疗效和耐药性的复杂相互作用因素的关键。

原始出处：

Michael D. Jain, et al. Whole-genome sequencing reveals complex genomic features underlying anti-CD19 CAR T-cell treatment failures in lymphoma. Blood (2022) 140 (5): 491–503. https://doi.org/10.1182/blood.2021015008

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2023-03-21 仁者大医

#CAR-#

58 0
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2022-08-20 zhaojie88

#全基因组测序#

60 0
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2022-08-20 zhouqu_8

#基因组测序#

49 0
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2022-08-20 ms1692810954239974

#全基因组#

53 0
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2022-08-19 xulv123

认真学习～～

50 0

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