Proliferative potential and response to nivolumab in clear cell renal cell carcinoma patients
Proliferative potential and response to nivolumab in clear cell renal cell carcinoma patients
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DOI：
10.1080/2162402x.2020.1773200
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发表时间：
2020-01-01
期刊：
影响因子：
7.2
通讯作者：
Morrison, Carl
中科院分区：
文献类型：
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作者：
Zhang, Tian;Pabla, Sarabjot;Morrison, Carl
背景：缺乏预测转移性肾细胞癌（mRCC）免疫治疗反应的生物标志物。PD-L1免疫组化是mRCC中免疫检查点抑制剂（ICI）的补充诊断，但已显示出最小的临床效用，并且未用于常规临床实践。结果：对于用纳武单抗作为标准护理治疗的56名患者，有2名完全应答和8名部分应答，应答率为17.9%。将细胞增殖分为三分位数，来自参考肿瘤组中10个增殖相关基因的平均表达，低增殖性肿瘤（62.5%）比中度（30.4%）或高度增殖性（8.9%）肿瘤更常见。中度增殖性肿瘤富含PD-L1阳性（41.2%），而增殖性较差的肿瘤（11.4%）。中度增殖性肿瘤（29.4%）的客观缓解率高于低度增殖性肿瘤（11.4%），但无统计学显著性（p = 0.11）。当细胞增殖和阴性PD-L1肿瘤比例评分相结合时，获得了具有统计学意义的结果（p = 0.048），表明增殖性差和PD-L1阴性肿瘤患者的缓解率非常低与中度增殖性PD-L1阴性肿瘤（30%）相比，中度增殖性PD-L1阴性肿瘤（6.5%）。细胞增殖在预测透明细胞mRCC患者对nivolumab的反应方面具有价值，特别是当与PD-L1表达相结合时。需要进一步的研究，包括增加无进展生存期（PFS）沿着以及足够把握度的亚组，以进一步支持这些结果。
Background: Biomarkers predicting immunotherapy response in metastatic renal cell cancer (mRCC) are lacking. PD-L1 immunohistochemistry is a complementary diagnostic for immune checkpoint inhibitors (ICIs) in mRCC, but has shown minimal clinical utility and is not used in routine clinical practice.Methods: Tumor specimens from 56 patients with mRCC who received nivolumab were evaluated for PD-L1, cell proliferation (targeted RNA-seq), and outcome.Results: For 56 patients treated with nivolumab as a standard of care, there were 2 complete responses and 8 partial responses for a response rate of 17.9%. Dividing cell proliferation into tertiles, derived from the mean expression of 10 proliferation-associated genes in a reference set of tumors, poorly proliferative tumors (62.5%) were more common than moderately (30.4%) or highly proliferative (8.9%) counterparts. Moderately proliferative tumors were enriched for PD-L1 positive (41.2%), compared to poorly proliferative counterparts (11.4%). Objective response for moderately proliferative (29.4%) tumors was higher than that of poorly (11.4%) proliferative counterparts, but not statistically significant (p = .11). When cell proliferation and negative PD-L1 tumor proportion scores were combined statistically significant results were achieved (p = .048), showing that patients with poorly proliferative and PD-L1 negative tumors have a very low response rate (6.5%) compared to moderately proliferative PD-L1 negative tumors (30%).Conclusions: Cell proliferation has value in predicting response to nivolumab in clear cell mRCC patients, especially when combined with PD-L1 expression. Further studies which include the addition of progression-free survival (PFS) along with sufficiently powered subgroups are required to further support these findings.