Impact of gefitinib in early stage treatment on circulating cytokines and lymphocytes for patients with advanced non-small cell lung cancer.
Impact of gefitinib in early stage treatment on circulating cytokines and lymphocytes for patients with advanced non-small cell lung cancer.
复制标题
DOI：
10.2147/ott.s112158
复制
发表时间：
2017
影响因子：
4
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Sheng J;Fang W;Liu X;Xing S;Zhan J;Ma Y;Huang Y;Zhou N;Zhao H;Zhang L
表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）对人体免疫系统的影响仍不明确。本研究阐明了吉非替尼对晚期非小细胞肺癌（NSCLC）患者的免疫调节作用及其相关预后意义。在基线和吉非替尼治疗4周后，从54名患者中采集外周血样本。测量循环淋巴细胞群和细胞因子水平。通过免疫组织化学（IHC）进行吉非替尼对程序性细胞死亡配体-1（PD-L1）表达影响的初步研究。吉非替尼治疗4周后，外周自然杀伤细胞和干扰素-γ（INF-γ）显著增加（分别为P=0.005和0.02）。此外，循环白细胞介素（IL）-6显著降低，尤其是在吉非替尼敏感的患者中（P<0.001）。基线时IL-6水平较高与无进展生存期较差独立相关。NSCLC标本的实验表明，在吉非替尼治疗4周后，PD-L1表达下调。总之，发现吉非替尼治疗可以改变循环细胞因子和淋巴细胞。吉非替尼治疗前后循环淋巴细胞、细胞因子甚至PD-L1 IHC表达的动态变化支持该药物对晚期NSCLC的特异性免疫调节作用。
The impact of epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs) on the human immune system remains undefined. This study illustrates the immunomodulatory effect of gefitinib in patients with advanced non-small cell lung cancer (NSCLC) and its relevant prognostic significance. Peripheral blood samples were collected from 54 patients at baseline and after 4 weeks of gefitinib treatment. Circulating lymphocyte populations and cytokine levels were measured. Pilot investigation of the impact of gefitinib on programmed cell death ligand-1 (PD-L1) expression was conducted by immunohistochemistry (IHC). A significant increase of peripheral natural killer cells and interferon-gamma (INF-γ) after 4 weeks of gefitinib treatment (P=0.005 and 0.02, respectively). In addition, circulating interleukin (IL)-6 was significantly decreased, especially in patients sensitive to gefitinib (P<0.001). Higher levels of IL-6 at baseline independently correlated with poorer progression-free survival. Experiments with NSCLC specimens illustrated that PD-L1 expression were downregulated after 4 weeks of gefitinib treatment. In summary, it was found that gefitinib treatment can alter circulating cytokines and lymphocytes. Dynamic changes of circulating lymphocytes, cytokines, and even PD-L1 IHC expression around gefitinib treatment support the specific immunomodulatory effect of this agent for advanced NSCLC.