Center for Molecular Imaging, Radiotherapy and Oncology, Institute for Experimental and Clinical Research, Université Catholique de Louvain, Brussels, Belgium.
Center for Molecular Imaging, Radiotherapy and Oncology, Institute for Experimental and Clinical Research, Université Catholique de Louvain, Brussels, Belgium; Radiation Oncology Department, St-Luc University Hospital, Brussels, Belgium.
Radiother Oncol. 2017 Sep;124(3):411-417. doi: 10.1016/j.radonc.2017.08.018. Epub 2017 Sep 12.
Clinical studies indicate that patients with HPV/p16-associated head & neck squamous cell carcinoma (HNSCC) represent a subgroup with a better prognosis and improved response to conventional radiotherapy. Involvement of immune-based factors has been hypothesized. In the present study, we investigated radiation-induced differences in release of damage associated molecular patterns (DAMPs), cytokines and activation of dendritic cells (DCs) in HPV-positive and negative HNSCC cancer cell lines.
Calreticulin (CRT) exposure was detected on cancer cell surface. ATP, HMGB1 and cytokines were measured in culture supernatants. Maturation marker CD83 surface exposure was determined on DCs after co-incubation with irradiated tumor cells.
There was no increase in DAMPs and cytokine profiles after radiation treatment and no difference between HPV+ and HPV- cell lines. The HPV/p16-positive SCC90 cells showed a trend for increased total CRT, HMGB1, and number of cytokines compared to all other cell lines. None of the irradiated cancer cell lines could affect DC maturation.
Radiation treatment did not increase immunogenicity of HNSCC cell lines assessed by membrane CRT, ATP, HMGB1, cytokines production, and by activation of immature DCs. There was no difference between HPV-positive and HPV-negative cell lines.
临床研究表明,HPV/p16 相关头颈部鳞状细胞癌(HNSCC)患者是预后较好、对常规放疗反应改善的亚组。免疫相关因素的参与已被假设。在本研究中,我们研究了 HPV 阳性和阴性 HNSCC 癌细胞系中辐射诱导的损伤相关分子模式(DAMPs)、细胞因子释放和树突状细胞(DC)激活的差异。
检测癌细胞表面钙网蛋白(CRT)的暴露。测量培养上清液中的 ATP、HMGB1 和细胞因子。与辐照肿瘤细胞共孵育后,测定 DC 上成熟标志物 CD83 的表面暴露。
辐射治疗后 DAMPs 和细胞因子谱没有增加,HPV+和 HPV-细胞系之间也没有差异。与所有其他细胞系相比,HPV/p16 阳性 SCC90 细胞显示出总 CRT、HMGB1 和细胞因子数量增加的趋势。没有一种辐照癌细胞系能够影响未成熟 DC 的成熟。
通过膜 CRT、ATP、HMGB1、细胞因子产生和未成熟 DC 的激活评估,辐射治疗并未增加 HNSCC 细胞系的免疫原性。HPV 阳性和 HPV 阴性细胞系之间没有差异。