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Annals of Surgical Oncology

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01-01-2006 | Original Article

Inhibition of Host Signal Transducer and Activator of Transcription Factor 6 Results in Cure With Cyclophosphamide and Interleukin 12 Immunotherapy

Authors: Jeffrey A. Norton, Michelle Li, Natalie C. Lee, Kangla Tsung

Published in: Annals of Surgical Oncology | Issue 1/2006

Abstract

Background

Interleukin (IL)-12 immunotherapy is highly effective against established immunogenic tumors. However, nonimmunogenic tumors fail to respond to IL-12 therapy. Analysis of tumor rejection of the immunogenic tumors shows that a preexisting antitumor immune response is required for an effective IL-12 response. It is not known whether this lack of a preexisting host antitumor immune response is a limiting factor for the lack of response to IL-12 therapy by nonimmunogenic tumors.

Methods

Experiments were done using the spontaneously arising nonimmunogenic metastatic murine breast 4T1 carcinoma in normal and STAT6 knockout BALB/c mice.

Results

4T1 is nonimmunogenic in normal mice, and established subcutaneous tumors are resistant to immunotherapy with cyclophosphamide (Cy) plus IL-12. However, in STAT6 knockout mice, 4T1 becomes immunogenic, and established 4T1 tumors are eradicated by Cy plus IL-12. Adoptive transfer of spleen cells from normal mice into STAT6 knockout mice before tumor inoculation reduces both the immunogenicity and response to Cy plus IL-12 immunotherapy of 4T1 in the recipient mice.

Conclusions

Cy plus IL-12 immunotherapy can eradicate nonimmunogenic tumors as long as a preexisting immunity is established in the tumor-bearing host. Furthermore, the STAT6 pathway is likely involved in the suppression of the development of host antitumor immunity.

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Title: Inhibition of Host Signal Transducer and Activator of Transcription Factor 6 Results in Cure With Cyclophosphamide and Interleukin 12 Immunotherapy
Authors: Jeffrey A. Norton
Michelle Li
Natalie C. Lee
Kangla Tsung
Publication date: 01-01-2006
Publisher: Springer New York
Published in: Annals of Surgical Oncology / Issue 1/2006
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/ASO.2006.03.514

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Inhibition of Host Signal Transducer and Activator of Transcription Factor 6 Results in Cure With Cyclophosphamide and Interleukin 12 Immunotherapy

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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