Haeggblom Linnea, Nordfors Cecilia, Tertipis Nikolaos, Bersani Cinzia, Ramqvist Torbjörn, Näsman Anders, Dalianis Tina
Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska (CCK), Karolinska University Hospital, 171 76 Stockholm, Sweden.
Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, 171 77 Stockholm, Sweden.
Int J Oncol. 2017 Apr;50(4):1423-1430. doi: 10.3892/ijo.2017.3916. Epub 2017 Mar 16.
Human papillomavirus (HPV) infection is a risk factor for oropharyngeal cancer, besides smoking and alcohol. Patients with HPV-positive tumors have a better prognosis than those with HPV-negative tumors. Furthermore, patients with HPV-positive tumors, with high CD8+ tumor infiltrating lymphocyte counts or absent/low human leukocyte antigen (HLA) class I expression have the best outcome. The latter is paradoxical, since HLA class I expression is important for tumor recognition. Below, the hypothesis that radiation therapy increases HLA class I expression was tested. HPV16 positive head and neck cancer cell lines UPCI-SCC-154, UPCI-SCC-090 and UM-SCC-47, and the HPV-negative cancer cell line UT-SCC-14, were treated with 2-10 Gray (Gy) and tested for HLA class I expression, cell cycle changes and apoptosis by flow cytometry. HPV16 E5, E7 and HLA-A mRNA expression was tested by quantitative PCR. A dose of 10 Gy resulted in a tendency of increased HLA class I cell surface expression for all cell lines and reached statistical significance for UPCI-SCC-154 and UPCI-SCC-090. There were, however, no significant changes in HLA-A mRNA expression in any of the cell lines, or HPV16 E5, or E7 mRNA expression for UPCI-SCC-47 and UPCI-SCC-154, while for UPCI-SCC-090 HPV16 E5 mRNA decreased. In all cell lines there was a shift towards G2/M phase and increased apoptosis after irradiation with 10 Gy. To conclude, irradiation with 10 Gy increased HLA class I expression in the HPV-positive cell lines UPCI-SCC-154 and UPCI-SCC-090. A similar tendency was observed for HPV-positive UM-SCC-47 and HPV-negative UT-SCC-14.
除吸烟和饮酒外,人乳头瘤病毒(HPV)感染是口咽癌的一个风险因素。HPV阳性肿瘤患者的预后比HPV阴性肿瘤患者更好。此外,HPV阳性肿瘤患者中,CD8 +肿瘤浸润淋巴细胞计数高或人类白细胞抗原(HLA)I类表达缺失/低的患者预后最佳。后者看似矛盾,因为HLA I类表达对肿瘤识别很重要。以下测试了放射治疗会增加HLA I类表达的假说。用2 - 10格雷(Gy)的剂量处理HPV16阳性头颈部癌细胞系UPCI - SCC - 154、UPCI - SCC - 090和UM - SCC - 47,以及HPV阴性癌细胞系UT - SCC - 14,并通过流式细胞术检测HLA I类表达、细胞周期变化和细胞凋亡。通过定量PCR检测HPV16 E5、E7和HLA - A mRNA表达。10 Gy的剂量导致所有细胞系HLA I类细胞表面表达有增加的趋势,对于UPCI - SCC - 154和UPCI - SCC - 090达到统计学意义。然而,任何细胞系中的HLA - A mRNA表达、UPCI - SCC - 47和UPCI - SCC - 154中的HPV16 E5或E7 mRNA表达均无显著变化,而对于UPCI - SCC - 090,HPV16 E5 mRNA减少。在所有细胞系中,照射10 Gy后细胞周期向G2/M期转变且细胞凋亡增加。总之,10 Gy的照射增加了HPV阳性细胞系UPCI - SCC - 154和UPCI - SCC - 090中的HLA I类表达。在HPV阳性的UM - SCC - 47和HPV阴性的UT - SCC - 14中也观察到了类似趋势。