Circulating T-cell receptor diversity as predictive biomarker for PARP inhibitors maintenance therapy in high grade serous ovarian cancer
Circulating T-cell receptor diversity as predictive biomarker for PARP inhibitors maintenance therapy in high grade serous ovarian cancer
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循环 T 细胞受体多样性作为高级别浆液性卵巢癌 PARP 抑制剂维持治疗的预测生物标志物
DOI：
10.1016/j.ygyno.2022.11.013
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发表时间：
2022
影响因子：
4.7
通讯作者：
Hong Zheng
中科院分区：
文献类型：
--
作者：
Tong Shu;Zhipeng Zhou;Jing Bai;Xiao Xiao;Min Gao;Nan Zhang;Hongguo Wang;Xuefeng Xia;Yunong Gao;Hong Zheng
作为癌症患者的预测性生物标志物，CD 34 T细胞受体（TCR）库的多样性越来越受到关注。然而，高级别浆液性卵巢癌（HGSOC）患者接受聚（ADP-核糖）聚合酶抑制剂（PARPi）维持治疗的TCR的特点及其预测意义仍然unknows.MethodsTwenty-seven HGSOC患者进行了分析，包括22例接受PARPi维持治疗和5例未治疗的患者作为对照。在基线以及暴露于PARPi后一个月和三个月收集外周血样品用于TCR测序。要确定是否TCR多样性与PARPi疗效，我们比较了谁收到PARPi和那些谁没有。ResultsFor患者接受PARPi治疗或不，我们评估了在PARPi维护和治疗前后的TCR库的相似性克隆丰度的变化。结果显示，接受PARPi的患者具有比未治疗病例更稳定的TCR库。接下来，我们将治疗组中TCR多样性与PARPi的疗效相关联。PARPi治疗3个月后TCR多样性的上升趋势与PFS较长（21.7 vs 7.4个月，风险比= 0.19，p < 0.001）和PARPi治疗应答较好（91.7%vs 25.0%，p = 0.004）相关。此外，我们发现，PARPi的有效性的预测值的主要特征是相当大的减少的高频T细胞clones.ConclusionWe建议，循环TCR的多样性可能是一个潜在的预测生物标志物PARPi维持治疗HGSOC。
ObjectiveT-cell receptor (TCR) repertoire diversity is getting increasing attention as a predictive biomarker in cancer patients. However, the characteristics of the TCR together with its predictive significance for high grade serous ovarian cancer (HGSOC) patients receiving poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance therapy remain unknown.MethodsTwenty-seven patients with HGSOC were analyzed including 22 patients receiving PARPi maintenance therapy and 5 untreated patients as control. Peripheral blood samples were collected for TCR sequencing at baseline as well as one month and three months after the exposure to PARPi. To determine whether TCR diversity was related to PARPi efficacy, we compared the TCR repertoire between patients who had received PARPi and those who had not.ResultsFor patients receiving PARPi treatment or not, we evaluated changes in clone abundance during PARPi maintenance and the similarity of the TCR repertoire before and after the treatment. The results revealed that patients receiving PARPi had TCR repertoires that were more stable than those of untreated cases. We next correlated TCR diversity with the efficacy of PARPi in the treatment group. The rising trend of TCR diversity after three months with PARPi treatment was associated with a longer PFS (21.7 vs 7.4 months, hazard ratio = 0.19,p< 0.001) and a better response to PARPi (91.7% vs 25.0%,p= 0.004). Furthermore, we discovered that the primary characteristic with predictive value for the effectiveness of PARPi is the considerable reduction of the high-frequency T cell clones.ConclusionWe suggested that the circulating TCR diversity could be a potential predictive biomarker for PARPi maintenance therapy in HGSOC.