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用HPV阳性宫颈肿瘤裂解物致敏的树突状细胞在迁移能力上优于未致敏的树突状细胞,并能诱导强烈的Th1反应。

Dendritic cells primed with HPV positive cervical tumor lysate are superior to unprimed DCs in migratory capacity and induce a potent Th1 response.

作者信息

Ramanathan Priya, Dhandapani Hemavathi, Jayakumar Hascitha, Ganeshrajah Selvaluxmy, Thangarajan Rajkumar

机构信息

Department of Molecular Oncology, Cancer Institute (WIA), India.

Department of Radiation Oncology, Cancer Institute (WIA), India.

出版信息

Hum Immunol. 2014 Dec;75(12):1216-24. doi: 10.1016/j.humimm.2014.09.020. Epub 2014 Oct 12.

Abstract

In this study, we assessed the efficacy of tumor lysate primed and unprimed monocyte derived mature dendritic cells (DCs) to trigger an effective anti-tumor immune response in cervical cancer patients who tested positive for human papilloma virus (HPV) DNA. Lysate primed and unprimed DCs were assessed for the expression of CD80, CD86, CD40, HLADR and CD83. The ability of DCs to migrate in response to the chemokines CCL19 and 21 as well as their ability to secrete IL12p40 was investigated. Mixed lymphocyte proliferation assays were used to assess DC stimulatory capacity and their ability to generate a Th1 response. Our results showed no difference in phenotypic expression between primed and unprimed DCs but both had significantly increased expression of the activation marker CD83 when compared to immature DCs. Importantly, the primed DCs showed significant (P value=0.03) IL-12p40 secretion and a superior migratory capacity towards CC19 and CCL21 (P value=0.04) compared to unprimed DCs even after cytokine withdrawal. Primed DCs showed superior stimulation of T cell proliferation (allogeneic and autologous) and secretion of IFN gamma (IFN-γ) than the unprimed DCs. Hence whole tumor lysate primed mature DCs could be potent immunotherapeutic adjuvants to standard treatment for cervical cancer.

摘要

在本研究中,我们评估了肿瘤裂解物致敏和未致敏的单核细胞来源的成熟树突状细胞(DCs)在人乳头瘤病毒(HPV)DNA检测呈阳性的宫颈癌患者中引发有效抗肿瘤免疫反应的功效。评估了裂解物致敏和未致敏DCs的CD80、CD86、CD40、HLADR和CD83的表达。研究了DCs对趋化因子CCL19和21作出反应的迁移能力及其分泌IL12p40的能力。采用混合淋巴细胞增殖试验评估DCs的刺激能力及其产生Th1反应的能力。我们的结果显示,致敏和未致敏DCs之间的表型表达没有差异,但与未成熟DCs相比,两者的活化标志物CD83的表达均显著增加。重要的是,即使在细胞因子撤除后,致敏DCs与未致敏DCs相比,仍显示出显著的(P值 = 0.03)IL-12p40分泌以及对CC19和CCL21的更强迁移能力(P值 = 0.04)。致敏DCs对T细胞增殖(同种异体和自体)的刺激以及IFNγ(IFN-γ)的分泌均优于未致敏DCs。因此,全肿瘤裂解物致敏的成熟DCs可能是宫颈癌标准治疗的有效免疫治疗佐剂。

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