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

被引:25
作者
Huang Jian [1 ,2 ]
Shen Fangrong [3 ]
Huang Haitao [4 ]
Ling Chunhua [1 ]
Zhang Guangbo [4 ]
机构
[1] Soochow Univ, Affiliated Hosp 1, Dept Resp, Suzhou 215007, Peoples R China
[2] Soochow Univ, Affiliated Hosp 1, Dept Emergency, Suzhou 215007, Peoples R China
[3] Soochow Univ, Affiliated Hosp 1, Clin Immunol Lab, Suzhou 215007, Peoples R China
[4] Soochow Univ, Affiliated Hosp 1, Dept Thorac Surg, Suzhou 215007, Peoples R China
基金
中国国家自然科学基金;
关键词
Th subset; prognosis; tumor microenvironment; NSCLC; IFN-GAMMA; LUNG-CANCER; CELLS; PLASTICITY; CYTOKINES; TH17; INTERLEUKIN-17; MECHANISMS; TREG; TH2;
D O I
10.18632/oncotarget.14471
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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-gamma(+)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-gamma 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.
引用
收藏
页码:13116 / 13125
页数:10
相关论文
共 32 条
  • [1] Functional diversity of helper T lymphocytes
    Abbas, AK
    Murphy, KM
    Sher, A
    [J]. NATURE, 1996, 383 (6603) : 787 - 793
  • [2] CD4+CD25-Foxp3- Th1 cells are the source of IL-10-mediated immune suppression in chronic cutaneous leishmaniasis
    Anderson, Charles F.
    Oukka, Mohammed
    Kuchroo, Vijay J.
    Sacks, David
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (02) : 285 - 297
  • [3] An interleukin-17-mediated paracrine network promotes tumor resistance to anti-angiogenic therapy
    Chung, Alicia S.
    Wu, Xiumin
    Zhuang, Guanglei
    Ngu, Hai
    Kasman, Ian
    Zhang, Jianhuan
    Vernes, Jean-Michel
    Jiang, Zhaoshi
    Meng, Y. Gloria
    Peale, Franklin V.
    Ouyang, Wenjun
    Ferrara, Napoleone
    [J]. NATURE MEDICINE, 2013, 19 (09) : 1114 - 1123
  • [4] The Th1 life cycle: molecular control of IFN-γ to IL-10 switching
    Cope, Andrew
    Le Friec, Gaelle
    Cardone, John
    Kemper, Claudia
    [J]. TRENDS IN IMMUNOLOGY, 2011, 32 (06) : 278 - 286
  • [5] The immunobiology of cancer immunosurveillance and immunoediting
    Dunn, GP
    Old, LJ
    Schreiber, RD
    [J]. IMMUNITY, 2004, 21 (02) : 137 - 148
  • [6] Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling
    Eyerich, Stefanie
    Eyerich, Kilian
    Pennino, Davide
    Carbone, Teresa
    Nasorri, Francesca
    Pallotta, Sabatino
    Cianfarani, Francesca
    Odorisio, Teresa
    Traidl-Hoffmann, Claudia
    Behrendt, Heidrun
    Durham, Stephen R.
    Schmidt-Weber, Carsten B.
    Cavani, Andrea
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2009, 119 (12) : 3573 - 3585
  • [7] The Alteration and Clinical Significance of Th1/Th2/Th17/Treg Cells in Patients with Multiple Myeloma
    Feng, Ping
    Yan, Ruhong
    Dai, Xiaoli
    Xie, Xiaofang
    Wen, Huiyan
    Yang, Shun
    [J]. INFLAMMATION, 2015, 38 (02) : 705 - 709
  • [8] Self-limitation of Th1-mediated inflammation by IFN-γ
    Feuerer, Markus
    Eulenburg, Katharina
    Loddenkemper, Christoph
    Hamann, Alf
    Huehn, Jochen
    [J]. JOURNAL OF IMMUNOLOGY, 2006, 176 (05) : 2857 - 2863
  • [9] Innate and adaptive immune cells in the tumor microenvironment
    Gajewski, Thomas F.
    Schreiber, Hans
    Fu, Yang-Xin
    [J]. NATURE IMMUNOLOGY, 2013, 14 (10) : 1014 - 1022
  • [10] Inter-relation of Th1, Th2, Th17 and Treg cytokines in oral cancer patients and their clinical significance
    Gaur, Poonam
    Singh, Avadhesh Kumar
    Shukla, Nootan K.
    Das, Satya N.
    [J]. HUMAN IMMUNOLOGY, 2014, 75 (04) : 330 - 337