Cetuximab therapy in head and neck cancer: immune modulation with interleukin-12 and other natural killer cell-activating cytokines.
Cetuximab therapy in head and neck cancer: immune modulation with interleukin-12 and other natural killer cell-activating cytokines.
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DOI：
10.1016/j.surg.2012.05.035
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发表时间：
2012-09
期刊：
影响因子：
3.8
通讯作者：
Carson, William E., III
中科院分区：
文献类型：
--
作者：
Luedke, Eric;Jaime-Ramirez, Alena Cristina;Bhave, Neela;Roda, Julie;Choudhary, Moaz Maqbool;Kumar, Bhavna;Teknos, Theodoros N.;Carson, William E., III
我们假设IL-12会通过激活NK细胞的FcR效应机制来增强抗HER1抗体西妥昔单抗对头颈鳞状细胞癌（SCCHN）的抗肿瘤活性。通过流式细胞术和免疫印迹分析，所有细胞系均显示 HER1 高表达。用 IL-12 对 NK 细胞进行 12 小时预处理，西妥昔单抗包被的 SCCHN 细胞系的 NK 细胞裂解显着增强（与西妥昔单抗相比，p=0.005）。 HPV 阳性和 HPV 阴性细胞系的裂解水平相似。其他 NK 细胞激活因子，如 IL-2、IL-15 和 IL-21 也增强了抗体依赖性细胞介导的细胞毒性 (ADCC)。 IL-12 和西妥昔单抗包被的肿瘤细胞的刺激诱导协同产生纳克水平的干扰素-γ（IFN-γ；比对照增加 >6 倍）（p<0.001）。 NK 细胞产生的趋化因子 MIP-1α、RANTES 和 IL-8 也有类似的效果。与对照组相比，西妥昔单抗和 IL-12 共刺激的 NK 细胞中 ERK 的磷酸化（对 FcR 功能至关重要）得到增强。在西妥昔单抗包被的 SCCHN 细胞存在的情况下，NK 细胞的细胞因子刺激会导致 NK 细胞介导的 ADCC 和细胞因子分泌增强，而与肿瘤细胞 HPV 状态无关。细胞因子给药可能是西妥昔单抗治疗 HER1 阳性头颈癌的有用佐剂。
We hypothesized that IL-12 would enhance the anti-tumor activity of the anti-HER1 antibody cetuximab against squamous cell carcinomas of the head and neck (SCCHN) by activating the FcR effector mechanisms of NK cells. All cell lines showed high expression of HER1 by flow cytometry and immunoblot analysis. NK cell lysis of cetuximab-coated SCCHN cell lines was markedly enhanced by 12 hr pre-treatment of NK cells with IL-12 (p=0.005 vs. cetuximab). Similar levels of lysis were noted for both HPV-positive and HPV-negative cell lines. Other NK cell-activating factors such as IL-2, IL-15 and IL-21 also enhanced antibody-dependent cell-mediated cytotoxicity (ADCC). The stimulus of IL-12 and cetuximab-coated tumor cells induced synergistic production of nanogram levels of interferon-gamma (IFN-γ; >6-fold increase over controls) (p<0.001). A similar effect was seen for NK cell production of the chemokines MIP-1α, RANTES and IL-8. Phosphorylation of ERK (critical for FcR functions) was enhanced in NK cells costimulated with cetuximab and IL-12 compared to controls. Cytokine stimulation of NK cells in the presence of cetuximab-coated SCCHN cells leads to enhanced NK cell-mediated ADCC and cytokine secretion independent of tumor cell HPV-status. Cytokine administration could be a useful adjuvant in the cetuximab treatment of HER1-positive head and neck cancer.
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DOI：
10.1007/s00262-009-0697-4
发表时间：
2009-11
期刊：
Cancer immunology, immunotherapy : CII
影响因子：
--
作者：
López-Albaitero A;Lee SC;Morgan S;Grandis JR;Gooding WE;Ferrone S;Ferris RL
通讯作者：
Ferris RL
DOI：
10.4049/jimmunol.1000328
发表时间：
2011-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jaime-Ramirez AC;Mundy-Bosse BL;Kondadasula S;Jones NB;Roda JM;Mani A;Parihar R;Karpa V;Papenfuss TL;LaPerle KM;Biller E;Lehman A;Chaudhury AR;Jarjoura D;Burry RW;Carson WE 3rd
通讯作者：
Carson WE 3rd
影响因子：
158.5
作者：
Bonner, JA;Harari, PM;Ang, KK
通讯作者：
Ang, KK
影响因子：
15.9
作者：
Parihar, R;Dierksheide, J;Carson, WE
通讯作者：
Carson, WE
影响因子：
5.7
作者：
Bekaii-Saab TS;Roda JM;Guenterberg KD;Ramaswamy B;Young DC;Ferketich AK;Lamb TA;Grever MR;Shapiro CL;Carson WE 3rd
通讯作者：
Carson WE 3rd