Huang Jian, Shen Fangrong, Huang Haitao, Ling Chunhua, Zhang Guangbo
Department of respiratory, The First Affiliated Hospital of Soochow University, Suzhou, 215007, China.
Department of Emergency, The First Affiliated Hospital of Soochow University, Suzhou, 215007, China.
Oncotarget. 2017 Feb 21;8(8):13116-13125. doi: 10.18632/oncotarget.14471.
CD4+Th subsets play an important role in tumor progression but their expression characteristics and clinical significance in human tumor microenvironment remains unclear. In this study, we aim to analyze the expression and clinical significance of tissue-infiltrating Th1, Th2 and Th17 in lung cancer by flow cytometry. We found that the frequency of CD3+CD4+IFN-γ+Th1 in tumor nest was significantly lower than that in tumor boundary, adjacent normal lung tissue or corresponding lymph node tissue; the frequency of CD3+CD4+IL-4+Th2 in tumor nest was significantly higher than that in tumor boundary, adjacent normal lung tissue or corresponding lymph node tissue; the frequency of CD3+CD4+IL-17+Th17 in tumor nest was significantly lower than that in tumor boundary, but not adjacent normal tissue or corresponding lymph node tissue. Survival analysis of 2-years survival after surgery showed that Th1high group was significantly lower compared with Th1low group; Th2high and Th17low is a good prognosis index compared with the Th2low and Th17high groups respectively, but this difference failed to significance. In addition, we also found that PD-1 expression showed a high level on lung tumor tissues and adjacent non- tumor tissue infiltrating T cells, and no significant difference was found between the two groups. However PD-L1 on CD45+CD14+mononcytes/macrophages in tumor tissue show a significantly higher level compared with that in adjacent nontumor tissues. In vitro stimulation experiments showed that IFN-γ could significantly increase PD-L1 expression on monocyte. In conclusion, we for the first time found Th1high is a poor indicator for prognosis of lung cancer.
CD4+T辅助细胞亚群在肿瘤进展中发挥重要作用，但其在人类肿瘤微环境中的表达特征及临床意义仍不清楚。在本研究中，我们旨在通过流式细胞术分析肺癌组织中浸润的Th1、Th2和Th17的表达及临床意义。我们发现，肿瘤巢中CD3+CD4+IFN-γ+Th1的频率显著低于肿瘤边界、相邻正常肺组织或相应淋巴结组织；肿瘤巢中CD3+CD4+IL-4+Th2的频率显著高于肿瘤边界、相邻正常肺组织或相应淋巴结组织；肿瘤巢中CD3+CD4+IL-17+Th17的频率显著低于肿瘤边界，但与相邻正常组织或相应淋巴结组织无差异。术后2年生存率分析显示，Th1高表达组显著低于Th1低表达组；与Th2低表达组和Th17高表达组相比，Th2高表达和Th17低表达分别是较好的预后指标，但差异无统计学意义。此外，我们还发现肺癌组织及相邻非肿瘤组织浸润性T细胞上PD-1表达均呈高水平，两组间无显著差异。然而，肿瘤组织中CD45+CD14+单核细胞/巨噬细胞上的PD-L1水平显著高于相邻非肿瘤组织。体外刺激实验表明，IFN-γ可显著增加单核细胞上PD-L1的表达。总之，我们首次发现Th1高表达是肺癌预后不良的指标。
