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01-05-2005 | Original Article

Tumor sensitivity to IFN-γ is required for successful antigen-specific immunotherapy of a transplantable mouse tumor model for HPV-transformed tumors

Authors: Mary E. Dominiecki, Gregory L. Beatty, Zhen-Kun Pan, Paul Neeson, Yvonne Paterson

Published in: Cancer Immunology, Immunotherapy | Issue 5/2005

Abstract

Purpose: Many human tumors lose responsiveness to IFN-γ, providing a possible mechanism for the tumor to avoid immune recognition and destruction. Here we investigate the importance of tumor responsiveness to IFN-γ in the successful immunotherapy of TC1 tumors that were immortalized with human papillomavirus proteins E6 and E7. Methods: To investigate the role of IFN-γ in vivo, we constructed a variant of TC1, TC1.mugR, that is unresponsive to IFN-γ due to overexpression of a dominant negative IFN-γ receptor. Results: Using recombinant Listeria monocytogenes that express HPV-16 E7 (Lm-LLO-E7) to stimulate an antitumor response, we demonstrate that sensitivity to IFN-γ is required for therapeutic efficacy in that Lm-LLO-E7 induces regression of TC1 tumors but not TC1.mugR. In addition, we show that tumor sensitivity to IFN-γ is not required for inhibition of tumor angiogenesis by Lm-LLO-E7 or for trafficking of CD4⁺ and CD8⁺ T cells to the tumor. However, it is required for penetration of lymphocytes into the tumor mass in vivo. Conclusions: Our findings identify a role for IFN-γ in immunity to TC1 tumors and show that loss of tumor responsiveness to IFN-γ poses a challenge to antigen-based immunotherapy.

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Title: Tumor sensitivity to IFN-γ is required for successful antigen-specific immunotherapy of a transplantable mouse tumor model for HPV-transformed tumors
Authors: Mary E. Dominiecki
Gregory L. Beatty
Zhen-Kun Pan
Paul Neeson
Yvonne Paterson
Publication date: 01-05-2005
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 5/2005
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-004-0610-0

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