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Medical Oncology

, 34:44 | Cite as

Irradiation enhances dendritic cell potential antitumor activity by inducing tumor cell expressing TNF-α

  • Lijia Chang
  • Zhengzheng Zhang
  • Fang Chen
  • Wen Zhang
  • Shuang Song
  • Shuxia SongEmail author
Original Paper

Abstract

Dendritic cells (DCs)-based tumor vaccines have shown to be the promising methods for inducing therapeutic antitumor response. However, DCs alone rarely carry curative antitumor activity, and the immunosuppressive microenvironment may contribute to this defect of DC vaccinal function. Irradiation in combination with DCs has been shown to promote immune-mediated tumor destruction in preclinical studies. However, little is known about how irradiation alters the tumor microenvironment, and what host pathways modulate the activity of administrated DCs. In this study, BALB/c mice and the 4T1 breast cancer cell line were used in a tumor-bearing model. The tumor-bearing mice were irradiated locally up to 10 Gy for 3 consecutive days or a single dose of 30 Gy using a cesium source. Studies of dynamic change of the tumor microenvironment in irradiated versus untreated tumors revealed that there was no obvious change on IL-10, IL-6 and TGF-β expression or production, whereas increased TNF-α level within the first 2 weeks of irradiation. The increased TNF-α level is exactly right timing window for DCs injection, corresponding to the significant elevation of intratumoral CD8+ T infiltration and the regression of tumor size. With attention to scheduling, combination X-ray with DCs i.t. injection may offer a practical strategy to improve treatment outcomes.

Keywords

Irradiation DC vaccine Tumor-bearing mice Microenvironment TNF-α 

Notes

Acknowledgements

This work was supported by a grant from the National Natural Science Foundation of China (81071710). We are grateful to Xuehui Yang for critical reading of the manuscript.

Compliance with ethical standards

Conflict of interest

Shuxia Song has received research grants from the National Natural Science Foundation of China (81071710). Authors declare that they have no conflict of interest.

Ethical approval

The mice were housed under specific pathogen-free conditions in the central animal facility of Hebei Medical University. All animal procedures were approved and performed in accordance with the animal guidelines of the Animal Care and Use Committee of Hebei Medical University.

Supplementary material

12032_2016_864_MOESM1_ESM.tif (101 kb)
Fig. 1 Irradiated 4T1 lysate pulsed DCs had advantage on antigen presentation. (A) Irradiated 4T1-lysate could not enhance DCs to secrete IL-12. (B) Naïve splenic cells were stimulated in vitro by irradiated versus non-irradiated 4T1 lysate pulsed-DCs at various ratios. In control samples containing splenic cells alone, DCs alone, and splenic cells co-cultured with unpulsed-DCs no IFN-γ secretion were detected. Data are reported as the average concentration of IFNγ (pg/ml) per 1×106 responders per 48 h ± SE of triplicate samples. *, P<0.05 (TIFF 100 kb)

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Lijia Chang
    • 1
  • Zhengzheng Zhang
    • 1
  • Fang Chen
    • 1
  • Wen Zhang
    • 1
  • Shuang Song
    • 1
  • Shuxia Song
    • 1
    Email author
  1. 1.Department of Immunology and Key Laboratory of Immune Mechanism and Intervention on Serious DiseaseHebei Medical UniversityShijiazhuangPeople’s Republic of China

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