Th1high in tumor microenvironment is an indicator of poor prognosis for patients with NSCLC

Abstract

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 Th1^high group was significantly lower compared with Th1^low group; Th2^high and Th17^low is a good prognosis index compared with the Th2^low and Th17^high 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 Th1^high is a poor indicator for prognosis of lung cancer.