Contribution of CD95 ligand-induced neutrophil infiltration to the bystander effect in p53 gene therapy for human cancer

T. Waku, Toshiyoshi Fujiwara, J. Shao, T. Itoshima, T. Murakami, M. Kataoka, S. Gomi, J. A. Roth, N. Tanaka

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Clinical trials of adenoviral p53 gene therapy provide the evidence that the bystander effect induced by the wild-type p53 gene transfer on adjacent tumor cells contributes to tumor progression; its mechanism, however, remains uncharacterized. We report in this work that injection of adenovirus expressing the human wild-type p53 gene (Ad5CMVp53) into established human colorectal tumors in nu/nu mice resulted in CD95 ligand (CD95L) overexpression, followed by a massive neutrophil infiltration. Culture supernatants of human colorectal cancer cells infected with Ad5CMVp53 exhibited a potent chemotactic activity against murine polymorphonuclear neutrophils, which could be abolished by the anti-CD95L mAb (NOK-1). In vivo cell depletion experiments indicated that neutrophils were in part responsible for the antitumor effect of the Ad5CMVp53 infection. Our data directly suggest that overexpression of CD95L by the wild-type p53 gene transfer induces neutrophil infiltration into human colorectal tumors, which may play a critical role in the bystander effect of p53 gene therapy.

Original languageEnglish
Pages (from-to)5884-5890
Number of pages7
JournalJournal of Immunology
Volume165
Issue number10
Publication statusPublished - Nov 15 2000

Fingerprint

Bystander Effect
Fas Ligand Protein
Neutrophil Infiltration
p53 Genes
Genetic Therapy
Colorectal Neoplasms
Neoplasms
Neutrophils
Human Adenoviruses
Clinical Trials
Injections
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

Waku, T., Fujiwara, T., Shao, J., Itoshima, T., Murakami, T., Kataoka, M., ... Tanaka, N. (2000). Contribution of CD95 ligand-induced neutrophil infiltration to the bystander effect in p53 gene therapy for human cancer. Journal of Immunology, 165(10), 5884-5890.

Contribution of CD95 ligand-induced neutrophil infiltration to the bystander effect in p53 gene therapy for human cancer. / Waku, T.; Fujiwara, Toshiyoshi; Shao, J.; Itoshima, T.; Murakami, T.; Kataoka, M.; Gomi, S.; Roth, J. A.; Tanaka, N.

In: Journal of Immunology, Vol. 165, No. 10, 15.11.2000, p. 5884-5890.

Research output: Contribution to journalArticle

Waku, T, Fujiwara, T, Shao, J, Itoshima, T, Murakami, T, Kataoka, M, Gomi, S, Roth, JA & Tanaka, N 2000, 'Contribution of CD95 ligand-induced neutrophil infiltration to the bystander effect in p53 gene therapy for human cancer', Journal of Immunology, vol. 165, no. 10, pp. 5884-5890.
Waku, T. ; Fujiwara, Toshiyoshi ; Shao, J. ; Itoshima, T. ; Murakami, T. ; Kataoka, M. ; Gomi, S. ; Roth, J. A. ; Tanaka, N. / Contribution of CD95 ligand-induced neutrophil infiltration to the bystander effect in p53 gene therapy for human cancer. In: Journal of Immunology. 2000 ; Vol. 165, No. 10. pp. 5884-5890.
@article{e4722e4259284a9795b0980a9f6ad3ca,
title = "Contribution of CD95 ligand-induced neutrophil infiltration to the bystander effect in p53 gene therapy for human cancer",
abstract = "Clinical trials of adenoviral p53 gene therapy provide the evidence that the bystander effect induced by the wild-type p53 gene transfer on adjacent tumor cells contributes to tumor progression; its mechanism, however, remains uncharacterized. We report in this work that injection of adenovirus expressing the human wild-type p53 gene (Ad5CMVp53) into established human colorectal tumors in nu/nu mice resulted in CD95 ligand (CD95L) overexpression, followed by a massive neutrophil infiltration. Culture supernatants of human colorectal cancer cells infected with Ad5CMVp53 exhibited a potent chemotactic activity against murine polymorphonuclear neutrophils, which could be abolished by the anti-CD95L mAb (NOK-1). In vivo cell depletion experiments indicated that neutrophils were in part responsible for the antitumor effect of the Ad5CMVp53 infection. Our data directly suggest that overexpression of CD95L by the wild-type p53 gene transfer induces neutrophil infiltration into human colorectal tumors, which may play a critical role in the bystander effect of p53 gene therapy.",
author = "T. Waku and Toshiyoshi Fujiwara and J. Shao and T. Itoshima and T. Murakami and M. Kataoka and S. Gomi and Roth, {J. A.} and N. Tanaka",
year = "2000",
month = "11",
day = "15",
language = "English",
volume = "165",
pages = "5884--5890",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "10",

}

TY - JOUR

T1 - Contribution of CD95 ligand-induced neutrophil infiltration to the bystander effect in p53 gene therapy for human cancer

AU - Waku, T.

AU - Fujiwara, Toshiyoshi

AU - Shao, J.

AU - Itoshima, T.

AU - Murakami, T.

AU - Kataoka, M.

AU - Gomi, S.

AU - Roth, J. A.

AU - Tanaka, N.

PY - 2000/11/15

Y1 - 2000/11/15

N2 - Clinical trials of adenoviral p53 gene therapy provide the evidence that the bystander effect induced by the wild-type p53 gene transfer on adjacent tumor cells contributes to tumor progression; its mechanism, however, remains uncharacterized. We report in this work that injection of adenovirus expressing the human wild-type p53 gene (Ad5CMVp53) into established human colorectal tumors in nu/nu mice resulted in CD95 ligand (CD95L) overexpression, followed by a massive neutrophil infiltration. Culture supernatants of human colorectal cancer cells infected with Ad5CMVp53 exhibited a potent chemotactic activity against murine polymorphonuclear neutrophils, which could be abolished by the anti-CD95L mAb (NOK-1). In vivo cell depletion experiments indicated that neutrophils were in part responsible for the antitumor effect of the Ad5CMVp53 infection. Our data directly suggest that overexpression of CD95L by the wild-type p53 gene transfer induces neutrophil infiltration into human colorectal tumors, which may play a critical role in the bystander effect of p53 gene therapy.

AB - Clinical trials of adenoviral p53 gene therapy provide the evidence that the bystander effect induced by the wild-type p53 gene transfer on adjacent tumor cells contributes to tumor progression; its mechanism, however, remains uncharacterized. We report in this work that injection of adenovirus expressing the human wild-type p53 gene (Ad5CMVp53) into established human colorectal tumors in nu/nu mice resulted in CD95 ligand (CD95L) overexpression, followed by a massive neutrophil infiltration. Culture supernatants of human colorectal cancer cells infected with Ad5CMVp53 exhibited a potent chemotactic activity against murine polymorphonuclear neutrophils, which could be abolished by the anti-CD95L mAb (NOK-1). In vivo cell depletion experiments indicated that neutrophils were in part responsible for the antitumor effect of the Ad5CMVp53 infection. Our data directly suggest that overexpression of CD95L by the wild-type p53 gene transfer induces neutrophil infiltration into human colorectal tumors, which may play a critical role in the bystander effect of p53 gene therapy.

UR - http://www.scopus.com/inward/record.url?scp=0034670020&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034670020&partnerID=8YFLogxK

M3 - Article

C2 - 11067949

AN - SCOPUS:0034670020

VL - 165

SP - 5884

EP - 5890

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 10

ER -