Cancer Immunology, Immunotherapy

, Volume 64, Issue 11, pp 1475–1485 | Cite as

Expression of TNFR2 by regulatory T cells in peripheral blood is correlated with clinical pathology of lung cancer patients

  • Fan Yan
  • Ruijuan Du
  • Feng Wei
  • Hua Zhao
  • Jinpu Yu
  • Changli Wang
  • Zhongli Zhan
  • Tingting Ding
  • Xiubao Ren
  • Xin ChenEmail author
  • Hui LiEmail author
Original Article


CD4+FoxP3+ regulatory T cells (Tregs) represent a major cellular mediator of cancer immune evasion. The expression of tumor necrosis factor receptor type II (TNFR2) on Tregs is reported to identify the maximally suppressive Treg population in both mice and human. We therefore investigated the phenotype and function of TNFR2+ Tregs present in the peripheral blood (PB) of 43 lung cancer patients. Further, the association of TNFR2 expression on Tregs with clinicopathological factors was analyzed. The results showed that in the PB of lung cancer patients, Tregs expressed markedly higher levels of TNFR2 than conventional T cells (Tconvs). Expression of TNFR2 appeared to correlate better than CD25+ and CD127 with FoxP3 expression. PB TNFR2+ Tregs in lung cancer patients were more proliferative and expressed higher levels of the immunosuppressive molecule CTLA-4, and consequently more potently suppressed IFNγ production by cocultured CD8 CTLs. More importantly, higher TNFR2 expression levels on Tregs were associated with lymphatic invasion, distant metastasis and more advanced clinical stage of lung cancer patients. Therefore, our study suggests that TNFR2+ Tregs play a role in promoting tumor progressive metastasis and expression of TNFR2 by PB Tregs may prove to be a useful prognostic marker in lung cancer patients.


CD4+FoxP3+ regulatory T cells Tumor necrosis factor receptor type II (TNFR2) Lung cancer Clinical pathology Immunosuppression 



Acute myeloid leukemia


Cytotoxic T lymphocytes


Cytotoxic T lymphocyte-associated antigen 4


Enzyme-linked immunosorbent assay


Forkhead box P3




Immunoglobulin G


Mean fluorescence intensity


Peripheral blood


Peripheral blood mononuclear cells


Conventional T cells


Transforming growth factor


Tumor necrosis factor


Tumor necrosis factor receptor type I


Tumor necrosis factor receptor type II


CD4+FoxP3+ regulatory T cells



This study was supported by grants from Natural Science Foundation of China (No. 81171983 and No. 81401888) and Tianjin Natural Science Foundation (No. 12JCYBJC16100). We honestly thank Dr. Joost J. Oppenheim for his critical review and comments that greatly improved the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare no financial or commercial conflict of interest.

Supplementary material

262_2015_1751_MOESM1_ESM.pdf (311 kb)
Supplementary material 1 (PDF 310 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Fan Yan
    • 1
    • 3
    • 4
  • Ruijuan Du
    • 1
    • 3
    • 4
  • Feng Wei
    • 1
    • 3
    • 4
  • Hua Zhao
    • 1
    • 3
    • 4
  • Jinpu Yu
    • 1
    • 3
    • 4
  • Changli Wang
    • 3
    • 6
  • Zhongli Zhan
    • 3
    • 7
  • Tingting Ding
    • 1
    • 3
    • 4
  • Xiubao Ren
    • 2
    • 3
    • 4
  • Xin Chen
    • 5
    Email author
  • Hui Li
    • 1
    • 3
    • 4
    Email author
  1. 1.Department of ImmunologyTianjin Medical University Cancer Institute & HospitalTianjinPeople’s Republic of China
  2. 2.Department of BiotherapyTianjin Medical University Cancer Institute & HospitalTianjinPeople’s Republic of China
  3. 3.National Clinical Research Center of CancerTianjinPeople’s Republic of China
  4. 4.Key Laboratory of Cancer Immunology and BiotherapyTianjinPeople’s Republic of China
  5. 5.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical SciencesUniversity of MacauTaipa, MacauPeople’s Republic of China
  6. 6.Department of Pulmonary OncologyTianjin Medical University Cancer Institute & HospitalTianjinPeople’s Republic of China
  7. 7.Department of PathologyTianjin Medical University Cancer Institute & HospitalTianjinPeople’s Republic of China

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