CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Analyses of peripheral blood NK cells in response to anti-PD-1 therapy in metastatic melanoma patients.
Analyses of peripheral blood NK cells in response to anti-PD-1 therapy in metastatic melanoma patients.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
程序性细胞死亡蛋白1（PD-1）轴的治疗性阻断可能增强抗肿瘤免疫，尤其是自然杀伤（NK）细胞活性。在32例BRAF野生型（wt）转移性黑色素瘤（MM）患者中，在PD-1抑制剂Pembrolizumab治疗前及每12周治疗后，我们通过流式细胞术分析了T细胞亚群、NK细胞和CD14 + HLA-DR - 单核细胞的百分比，CD107a脱颗粒标志物的表达，以及NK细胞上活化性NKG2D、NKp46、DNAM-1和抑制性CD158a受体的表达，直至一年或疾病进展（DP）。与治疗前数值相比，疾病控制患者（非DP患者）在Pembrolizumab治疗期间淋巴细胞计数、NK细胞百分比显著增加，CD107a、NKG2D、NKp46表达增加，但NK细胞上CD158a降低。DP患者中性粒细胞数量增加，免疫抑制性CD14 + HLA-DR - 单核细胞百分比增加，以及NK细胞上CD158a表达增加。在疾病控制的MM患者中，与DP患者相反，阻断PD-1抑制性分子可能通过增强NK细胞脱颗粒和活化性受体表达来增加NK细胞细胞毒性。
因此，我们的研究结果表明，MM患者中的NK细胞及其受体可能是对Pembrolizumab应答的潜在生物标志物。
Therapeutical blockade of programmed cell death protein 1 (PD-1) axis may enhance anti-tumor immunity and especially natural killer (NK) cells activity. In 32 BRAF wild type (wt) metastatic melanoma (MM) patients before and after every 12 weeks of therapy with PD-1 inhibitor, Pembrolizumab, we analyzed the percentage of T cell subsets, NK cells and CD14 + HLA-DR - monocytes, the expression of CD107a degranulation marker, activating NKG2D, NKp46, DNAM-1 and inhibitory CD158a receptors on NK cells by Flow cytometry, until one year or disease progression (DP).
The patients with disease control (non-DP patients) had significant increase in lymphocyte count, percentage of NK cells, increased expression of CD107a, NKG2D, NKp46, but decreased CD158a on NK cells during Pembrolizumab therapy compared to pretherapy values.
Patients with DP had increased neutrophil number, increased percentage of immunosuppressive CD14 + HLA-DR - monocytes, as well as increased CD158a expression on NK cells. In MM patients with disease control, contrary to DP patients blocking of PD-1 inhibitory molecule may increase NK cell cytotoxicity through enhancement of NK cell degranulation and activating receptor expression.
Therefore, our findings show that NK cells and their receptors in MM patients may be potential biomarkers of response to Pembrolizumab.
MEMBER ACCOUNT
登录成功会直接打开下一页。
