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Cancer Immunology, Immunotherapy

, Volume 62, Issue 9, pp 1439–1451 | Cite as

Increased CD14+HLA-DR-/low myeloid-derived suppressor cells correlate with extrathoracic metastasis and poor response to chemotherapy in non-small cell lung cancer patients

  • Ang Huang
  • Bo Zhang
  • Bo Wang
  • Fan Zhang
  • Ke-Xing FanEmail author
  • Ya-Jun GuoEmail author
Original Article

Abstract

Accumulating evidence has demonstrated that myeloid-derived suppressor cells (MDSCs), a heterogeneous population of cells, play an important role in the subversion, inhibition, and downregulation of the immune response to cancer. However, the characteristics of these cells, particularly clinical relevance, in malignant tumors remain unclear due to a lack of specific markers. In this study, we characterized peripheral CD14+HLA-DR-/low cells, a new human MDSC subpopulation, in 89 patients with non-small cell lung cancer (NSCLC). As expected, both frequency and absolute number of CD14+HLA-DR-/low cells were significantly increased in the peripheral blood of NSCLC patients compared with that of the healthy controls and indicated an association with metastasis, response to chemotherapy, and progression-free survival. These cells showed decreased expression of CD16 and CD86 compared with HLA-DR+ monocytes. Unlike classical monocytes, these populations showed significantly decreased allostimulatory activity and showed the ability to inhibit autologous T cell proliferation and IFN-γ production in a cell-contact-dependent manner. Furthermore, we demonstrated that CD14+HLA-DR-/low cells expressed the NADPH oxidase component gp91phox and generated high level of reactive oxygen species (ROS). Moreover, inactivation of ROS reversed their immunosuppressive capacity on T cell response. These results prove, for the first time, the existence of ROS-producing CD14+HLA-DR-/low myeloid-derived suppressor cells in NSCLC patients, which mediate tumor immunosuppression and might thus represent a potential target for therapeutic intervention.

Keywords

Non-small cell lung cancer  HLA-DR expression  Myeloid-derived suppressor cells  Immunosuppression  Tumor immunity 

Abbreviations

MDSCs

Myeloid-derived suppressor cells

AS

Adenocarcinoma

SCC

Squamous cell carcinoma

RECIST

Response Evaluation Criteria in Solid Tumors

PFS

Progression-free survival

L-NMMA

NG-Methyl-l-arginine acetate salt

nor-NOHA

Nω-Hydroxy-nor-l-arginine, diacetate salt

CD14depl

CD14-depleted

Arg1

Arginase-1

iNOS

Inducible nitric oxide synthase

Cox2

Cyclooxygenase 2

IDO

Indoleamine 2, 3-dioxygenase

NADPH

Nicotinamide adenine dinucleotide phosphate

DCF

2′,7′-dichlorofluorescein

ROS

Reactive oxygen species

Notes

Acknowledgments

This study was supported by grants from the Ministry of Science and Technology of China (“973” projects) (No. 2012CB917104) and the National Natural Science Foundation of China (No. 81172853 and No. 81201605).

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

262_2013_1450_MOESM1_ESM.pdf (2.6 mb)
Supplementary material 1 (PDF 2651 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Cancer CenterChinese PLA General HospitalBeijingPeople’s Republic of China
  2. 2.International Joint Cancer InstituteThe Second Military Medical UniversityShanghaiPeople’s Republic of China
  3. 3.Department of Infectious DiseasesBeijing 302 HospitalBeijingPeople’s Republic of China

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