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The effects of FasL on inflammation and tumor survival are dependent on its expression levels

Cancer Gene Therapy volume 14, pages 262–267 (2007)Cite this article

Abstract

The apoptosis-inducing Fas ligand (FasL) is expressed in a variety of human cancers and has been implicated in tumor immune evasion. Paradoxically, ectopic expression of FasL in experimental tumors triggers a neutrophil-mediated inflammatory response and tumor rejection. To resolve these conflicting findings, we have established B16 melanoma and P29 Lewis lung carcinoma lines expressing different levels of FasL and examined their tumorigenicity in vivo. While tumors with a high level of FasL were rapidly rejected as previously reported, those expressing a low level of FasL were not rejected but grew faster than did FasL-negative parental cells. The growth enhancement of FasLlow tumors was not observed in T-cell-deficient nude mice, suggesting that FasL expressed in tumors at low levels counteracted against T-cell-dependent antitumor responses. In support of this notion, FasLlow tumors were found to grow faster than parental cells in mice that had acquired tumor-specific immunity. Furthermore, histological examinations revealed apoptosis of lymphocytes in tissue sections of FasLlow tumors. These results collectively suggest that FasL on tumors is a double-edged sword: at high levels it triggers tumor rejection whereas at low levels it facilitates tumor growth possibly by suppressing antitumor immune responses.

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Abbreviations

FasL:

Fas ligand

CD40L:

CD40 ligand

PI:

propidium iodide

TUNEL:

terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling

H&E:

hematoxylin and eosin

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Acknowledgements

We thank Satoko Miyauchi for secretary assistance. This work was supported by Grants-in-aid for the 21st Century Center of Excellent (COE) Program of the Japanese Ministry of Education, Culture, Sports, Science and Technology, grant-in-aid for scientific research from Japan Society for the Promotion of Science and grant-in-aid from the Tsuchiya Foundation and the Futaba Electronics Memorial Foundation.

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Author notes

  1. A Wada and Y Tada: The first two authors contributed equally to this study.

Authors and Affiliations

  1. Division of Pathology, Chiba Cancer Center Research Institute, Chiba, Japan

    A Wada, Y Tada, K Kawamura, J O-Wang & M Tagawa

  2. Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan

    A Wada, Y Tada, Y Takiguchi, K Tatsumi & T Kuriyama

  3. Division of Surgical Pathology, Chiba Cancer Center, Chiba, Japan

    T Takenouchi

  4. Laboratory for Antigen Receptor Diversity, Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Kanagawa, Japan

    J O-Wang

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  1. A Wada
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  3. K Kawamura
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  4. Y Takiguchi
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Corresponding author

Correspondence to M Tagawa.

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Wada, A., Tada, Y., Kawamura, K. et al. The effects of FasL on inflammation and tumor survival are dependent on its expression levels. Cancer Gene Ther 14, 262–267 (2007). https://doi.org/10.1038/sj.cgt.7701008

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  • DOI: https://doi.org/10.1038/sj.cgt.7701008

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