Increase of lymphocytes and eosinophils, and decrease of neutrophils at an early stage of anti-PD-1 antibody treatment is a favorable sign for advanced malignant melanoma
Increase of lymphocytes and eosinophils, and decrease of neutrophils at an early stage of anti-PD-1 antibody treatment is a favorable sign for advanced malignant melanoma
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DOI：
10.5582/ddt.2020.03043
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发表时间：
2020-01-01
影响因子：
3.1
通讯作者：
Kadono, Takafumi
中科院分区：
文献类型：
--
作者：
Ohashi, Hiroyuki;Takeuchi, Sora;Kadono, Takafumi
免疫检查点抑制剂（如抗PD-1抗体）的出现对晚期恶性黑色素瘤的治疗产生了显著影响。然而，只有不到一半的患者从这些抗体中受益，迫切需要能够灵敏地区分反应者和非反应者的生物标志物。在本文中，我们通过回顾性分析来自用纳武单抗和派姆单抗治疗的晚期恶性黑色素瘤患者的临床数据来探索这些生物标志物。我们发现抗PD-1抗体对仅转移到软组织的患者特别有效。虽然在应答者和非应答者之间的相对中性粒细胞计数（RNC）、相对淋巴细胞计数（RLC）、中性粒细胞与淋巴细胞比率（NLR）和相对嗜酸性粒细胞计数（REC）的基线值中未发现显著差异，但抗PD-1治疗后的应答者显示在治疗的前6周内淋巴细胞和嗜酸性粒细胞增加，中性粒细胞减少。计算治疗后3周和6周RNC和RLC的变化，分别记为N Delta 3-L Delta 3和N Delta 6-L Delta 6。在应答者中，N Delta 3-L Delta 3显著降低，这表明早在抗PD-1治疗3周后中性粒细胞减少和淋巴细胞增加可能是有用的临床指标。此外，应答者和非应答者之间的N Delta 6-L Delta 6的差异甚至更稳健。这些数据表明，RNC、RLC和REC的变化以及N Delta 3-L Delta 3和N Delta 6-L Delta 6的组合可能是抗PD-1治疗的早期和敏感生物标志物的有用工具。
The advent of immune checkpoint inhibitors such as anti-PD-1 antibodies had a striking impact on the treatment for advanced malignant melanoma. However, less than half of the patients benefited from those antibodies, and biomarkers that could sensitively differentiate responders from non-responders are urgently needed. Herein, we explored such biomarkers by retrospectively analyzing clinical data from patients with advanced malignant melanoma treated with nivolumab and pembrolizumab. We found that anti-PD-1 antibody was especially effective for those with metastasis only to soft tissues. Although no significant difference was found in the baseline value of relative neutrophil count (RNC), relative lymphocyte count (RLC), neutrophil to lymphocyte ratio (NLR), and relative eosinophil count (REC) between responders and non-responders, responders after anti-PD-1 therapy revealed the increase of lymphocytes and eosinophils and the decrease of neutrophils within the first 6 weeks of the treatment. We also calculated the change of RNC and RLC 3 weeks and 6 weeks after the initiation of the therapy and designated as N Delta 3-L Delta 3 and N Delta 6-L Delta 6 respectively. N Delta 3-L Delta 3 was significantly decreased in responders, which suggest that the neutrophil decrease and lymphocyte increase after as early as 3 weeks of anti-PD-1 therapy might be a useful clinical indicator. In addition, the difference of N Delta 6-L Delta 6 between responders and non-responders was even more robust. These data suggest that change of RNC, RLC, and REC together with the combination of N Delta 3-L Delta 3 and N Delta 6-L Delta 6 might be a useful tool for early and sensitive biomarkers for anti-PD-1 therapy.