University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, 22 South Greene Street, Baltimore, MD, 21201, USA.
University of Pittsburgh Medical Center Hillman Cancer Center, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA.
Lung Cancer. 2018 Sep;123:87-90. doi: 10.1016/j.lungcan.2018.06.028. Epub 2018 Jun 26.
Co-signaling molecules PD-L1, B7-H3, and PD-1 play a key role in cancer immunology. There are limited but emerging data on expression of these molecules in HIV-infected lung cancer patients.
We reviewed archived lung cancer tissue samples from HIV-infected cases (n = 13) and HIV-uninfected controls (n = 13) from 2001-2015. Cases and controls were matched by histology and stage. Immunostained tumor sections were analyzed for percent of tumor cells expressing PD-L1 and B7-H3, and percent of tumor infiltrating immune cells (TII) expressing PD-1 and PD-L1. Positive expression was defined as >5%. Statistical analysis was performed using the non-parametric Mann-Whitney test and the chi-square test.
PD-L1 expression on tumor cells was positive in 23% of cases and 46% of controls. B7-H3 expression on tumor cells was positive in 92% of cases and 69% of controls. PD-1 expression on TII was positive in 69% of cases and 54% of controls. PD-L1 expression on TII was positive in 31% of cases and 69% of controls. B7-H3 percent expression on tumor cells was significantly higher in cases vs. controls (median 90% vs 20%, p = 0.005), but there were no significant differences in percent expression of PD-L1 on tumor cells, PD-1 on TII or PD-L1 on TII.
HIV-infected lung cancer patients had significantly higher B7-H3 tumor expression compared to HIV-uninfected controls, with similar rates of tumor PD-L1 expression, as well as PD-1 and PD-L1 expression on TII. These results support inclusion of HIV-infected lung cancer patients in future immunotherapy trials.
共刺激分子 PD-L1、B7-H3 和 PD-1 在癌症免疫学中发挥着关键作用。目前，关于这些分子在感染 HIV 的肺癌患者中的表达情况的数据有限，但正在不断涌现。
我们回顾了 2001 年至 2015 年间存档的 HIV 感染肺癌病例（n=13）和 HIV 未感染对照（n=13）的肺癌组织样本。病例和对照按照组织学和分期进行匹配。对免疫染色肿瘤切片进行分析，以确定 PD-L1 和 B7-H3 阳性肿瘤细胞的百分比，以及 PD-1 和 PD-L1 阳性肿瘤浸润免疫细胞（TII）的百分比。阳性表达定义为>5%。使用非参数 Mann-Whitney 检验和卡方检验进行统计分析。
肿瘤细胞 PD-L1 表达阳性的病例占 23%，对照占 46%。肿瘤细胞 B7-H3 表达阳性的病例占 92%，对照占 69%。TII 上 PD-1 表达阳性的病例占 69%，对照占 54%。TII 上 PD-L1 表达阳性的病例占 31%，对照占 69%。肿瘤细胞 B7-H3 表达阳性的病例明显高于对照（中位数 90%比 20%，p=0.005），但肿瘤细胞 PD-L1 表达阳性、TII 上 PD-1 表达阳性和 TII 上 PD-L1 表达阳性的病例百分比差异无统计学意义。
与 HIV 未感染对照相比，HIV 感染的肺癌患者肿瘤中 B7-H3 的表达明显更高，而肿瘤 PD-L1 表达以及 TII 上 PD-1 和 PD-L1 表达率相似。这些结果支持将 HIV 感染的肺癌患者纳入未来的免疫治疗试验。
