Tumor sensitivity to IFN-γ is required for successful antigen-specific immunotherapy of a transplantable mouse tumor model for HPV-transformed tumors
Many human tumors lose responsiveness to IFN-gamma, providing a possible mechanism for the tumor to avoid immune recognition and destruction. Here we investigate the importance of tumor responsiveness to IFN-gamma in the successful immunotherapy of TC1 tumors that were immortalized with human papill...
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| Veröffentlicht in: | Cancer Immunology, Immunotherapy Immunotherapy, 2005-05, Vol.54 (5), p.477-488 |
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| creator | DOMINIECKI, Mary E BEATTY, Gregory L PAN, Zhen-Kun NEESON, Paul PATERSON, Yvonne |
| description | Many human tumors lose responsiveness to IFN-gamma, providing a possible mechanism for the tumor to avoid immune recognition and destruction. Here we investigate the importance of tumor responsiveness to IFN-gamma in the successful immunotherapy of TC1 tumors that were immortalized with human papillomavirus proteins E6 and E7.
To investigate the role of IFN-gamma in vivo, we constructed a variant of TC1, TC1.mugR, that is unresponsive to IFN-gamma due to overexpression of a dominant negative IFN-gamma receptor.
Using recombinant Listeria monocytogenes that express HPV-16 E7 (Lm-LLO-E7) to stimulate an antitumor response, we demonstrate that sensitivity to IFN-gamma 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-gamma 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.
Our findings identify a role for IFN-gamma in immunity to TC1 tumors and show that loss of tumor responsiveness to IFN-gamma poses a challenge to antigen-based immunotherapy. |
| doi_str_mv | 10.1007/s00262-004-0610-0 |
| format | Article |
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To investigate the role of IFN-gamma in vivo, we constructed a variant of TC1, TC1.mugR, that is unresponsive to IFN-gamma due to overexpression of a dominant negative IFN-gamma receptor.
Using recombinant Listeria monocytogenes that express HPV-16 E7 (Lm-LLO-E7) to stimulate an antitumor response, we demonstrate that sensitivity to IFN-gamma 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-gamma 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.
Our findings identify a role for IFN-gamma in immunity to TC1 tumors and show that loss of tumor responsiveness to IFN-gamma poses a challenge to antigen-based immunotherapy.</description><identifier>ISSN: 0340-7004</identifier><identifier>EISSN: 1432-0851</identifier><identifier>DOI: 10.1007/s00262-004-0610-0</identifier><identifier>PMID: 15750832</identifier><identifier>CODEN: CIIMDN</identifier><language>eng</language><publisher>Berlin: Springer</publisher><subject>Animals ; Antigens, Neoplasm - genetics ; Antigens, Neoplasm - immunology ; Antineoplastic agents ; Bacterial Vaccines - therapeutic use ; Biological and medical sciences ; Cancer Vaccines - immunology ; Cancer Vaccines - therapeutic use ; Cell Line, Tumor ; Cell Transformation, Viral ; Disease Models, Animal ; Female ; Human papillomavirus ; Interferon-gamma - physiology ; Listeria monocytogenes ; Listeria monocytogenes - genetics ; Listeria monocytogenes - immunology ; Lymphocytes, Tumor-Infiltrating - immunology ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; Neoplasms, Experimental - drug therapy ; Neoplasms, Experimental - genetics ; Neoplasms, Experimental - immunology ; Oncogene Proteins, Viral - genetics ; Oncogene Proteins, Viral - immunology ; Original ; Papillomaviridae - genetics ; Papillomavirus E7 Proteins ; Papillomavirus Infections - drug therapy ; Papillomavirus Infections - genetics ; Papillomavirus Infections - immunology ; Pharmacology. Drug treatments ; Receptors, Interferon - genetics ; Receptors, Interferon - metabolism ; T-Lymphocytes, Cytotoxic - immunology ; Transcriptional Activation ; Tumor Escape - immunology ; Uterine Cervical Neoplasms - virology</subject><ispartof>Cancer Immunology, Immunotherapy, 2005-05, Vol.54 (5), p.477-488</ispartof><rights>2005 INIST-CNRS</rights><rights>Springer-Verlag 2004</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11032979/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11032979/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16630388$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15750832$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>DOMINIECKI, Mary E</creatorcontrib><creatorcontrib>BEATTY, Gregory L</creatorcontrib><creatorcontrib>PAN, Zhen-Kun</creatorcontrib><creatorcontrib>NEESON, Paul</creatorcontrib><creatorcontrib>PATERSON, Yvonne</creatorcontrib><title>Tumor sensitivity to IFN-γ is required for successful antigen-specific immunotherapy of a transplantable mouse tumor model for HPV-transformed tumors</title><title>Cancer Immunology, Immunotherapy</title><addtitle>Cancer Immunol Immunother</addtitle><description>Many human tumors lose responsiveness to IFN-gamma, providing a possible mechanism for the tumor to avoid immune recognition and destruction. Here we investigate the importance of tumor responsiveness to IFN-gamma in the successful immunotherapy of TC1 tumors that were immortalized with human papillomavirus proteins E6 and E7.
To investigate the role of IFN-gamma in vivo, we constructed a variant of TC1, TC1.mugR, that is unresponsive to IFN-gamma due to overexpression of a dominant negative IFN-gamma receptor.
Using recombinant Listeria monocytogenes that express HPV-16 E7 (Lm-LLO-E7) to stimulate an antitumor response, we demonstrate that sensitivity to IFN-gamma 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-gamma 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.
Our findings identify a role for IFN-gamma in immunity to TC1 tumors and show that loss of tumor responsiveness to IFN-gamma poses a challenge to antigen-based immunotherapy.</description><subject>Animals</subject><subject>Antigens, Neoplasm - genetics</subject><subject>Antigens, Neoplasm - immunology</subject><subject>Antineoplastic agents</subject><subject>Bacterial Vaccines - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Cancer Vaccines - immunology</subject><subject>Cancer Vaccines - therapeutic use</subject><subject>Cell Line, Tumor</subject><subject>Cell Transformation, Viral</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Human papillomavirus</subject><subject>Interferon-gamma - physiology</subject><subject>Listeria monocytogenes</subject><subject>Listeria monocytogenes - genetics</subject><subject>Listeria monocytogenes - immunology</subject><subject>Lymphocytes, Tumor-Infiltrating - immunology</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Neoplasm Transplantation</subject><subject>Neoplasms, Experimental - drug therapy</subject><subject>Neoplasms, Experimental - genetics</subject><subject>Neoplasms, Experimental - immunology</subject><subject>Oncogene Proteins, Viral - genetics</subject><subject>Oncogene Proteins, Viral - immunology</subject><subject>Original</subject><subject>Papillomaviridae - genetics</subject><subject>Papillomavirus E7 Proteins</subject><subject>Papillomavirus Infections - drug therapy</subject><subject>Papillomavirus Infections - genetics</subject><subject>Papillomavirus Infections - immunology</subject><subject>Pharmacology. Drug treatments</subject><subject>Receptors, Interferon - genetics</subject><subject>Receptors, Interferon - metabolism</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>Transcriptional Activation</subject><subject>Tumor Escape - immunology</subject><subject>Uterine Cervical Neoplasms - virology</subject><issn>0340-7004</issn><issn>1432-0851</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkc2OFSEQhYnRONfRB3Bj2OgOLaChYWXMxPlJJupidNuhucUMprvpaehJ7ov4Ir6HzzR4vf6tKDhfzqmiCHnO4TUHaN9kAKEFA2gYaA4MHpANb2R9MYo_JBuQDbC2ykfkSc5fayHA2sfkiKtWgZFiQ75drWNaaMYpxxLvYtnRkujF6Qf24zuNmS54u8YFtzT8pFbvMeewDtRNJV7jxPKMPoboaRzHdUrlBhc372gK1NGyuCnPQ0VdPyAd05qRln3emLY47D3PP31he7Bexpqz1_NT8ii4IeOzw3lMPp--vzo5Z5cfzy5O3l2yWQpdGBqrAI2xAhVujeC2cboPGIRonVVch9C0wUtueyt9MJxL3-pt0zsAp3gvj8nbX77z2td0j1PtZejmJY5u2XXJxe5_ZYo33XW66zgHKWxrq8Org8OSblfMpRtj9jjUsbEO3PFWqUZoVcEX_0b9yfi9iwq8PAAuezeE-ik-5r-c1hKkMfIeC9aecA</recordid><startdate>20050501</startdate><enddate>20050501</enddate><creator>DOMINIECKI, Mary E</creator><creator>BEATTY, Gregory L</creator><creator>PAN, Zhen-Kun</creator><creator>NEESON, Paul</creator><creator>PATERSON, Yvonne</creator><general>Springer</general><general>Springer-Verlag</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7T5</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>20050501</creationdate><title>Tumor sensitivity to IFN-γ is required for successful antigen-specific immunotherapy of a transplantable mouse tumor model for HPV-transformed tumors</title><author>DOMINIECKI, Mary E ; BEATTY, Gregory L ; PAN, Zhen-Kun ; NEESON, Paul ; PATERSON, Yvonne</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p326t-e8950e8892e5ed82194a6bfef227a9516ff47fc319b93cf8113c76d4ba00a51b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Antigens, Neoplasm - genetics</topic><topic>Antigens, Neoplasm - immunology</topic><topic>Antineoplastic agents</topic><topic>Bacterial Vaccines - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Cancer Vaccines - immunology</topic><topic>Cancer Vaccines - therapeutic use</topic><topic>Cell Line, Tumor</topic><topic>Cell Transformation, Viral</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>Human papillomavirus</topic><topic>Interferon-gamma - physiology</topic><topic>Listeria monocytogenes</topic><topic>Listeria monocytogenes - genetics</topic><topic>Listeria monocytogenes - immunology</topic><topic>Lymphocytes, Tumor-Infiltrating - immunology</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Neoplasm Transplantation</topic><topic>Neoplasms, Experimental - drug therapy</topic><topic>Neoplasms, Experimental - genetics</topic><topic>Neoplasms, Experimental - immunology</topic><topic>Oncogene Proteins, Viral - genetics</topic><topic>Oncogene Proteins, Viral - immunology</topic><topic>Original</topic><topic>Papillomaviridae - genetics</topic><topic>Papillomavirus E7 Proteins</topic><topic>Papillomavirus Infections - drug therapy</topic><topic>Papillomavirus Infections - genetics</topic><topic>Papillomavirus Infections - immunology</topic><topic>Pharmacology. Drug treatments</topic><topic>Receptors, Interferon - genetics</topic><topic>Receptors, Interferon - metabolism</topic><topic>T-Lymphocytes, Cytotoxic - immunology</topic><topic>Transcriptional Activation</topic><topic>Tumor Escape - immunology</topic><topic>Uterine Cervical Neoplasms - virology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>DOMINIECKI, Mary E</creatorcontrib><creatorcontrib>BEATTY, Gregory L</creatorcontrib><creatorcontrib>PAN, Zhen-Kun</creatorcontrib><creatorcontrib>NEESON, Paul</creatorcontrib><creatorcontrib>PATERSON, Yvonne</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer Immunology, Immunotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>DOMINIECKI, Mary E</au><au>BEATTY, Gregory L</au><au>PAN, Zhen-Kun</au><au>NEESON, Paul</au><au>PATERSON, Yvonne</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tumor sensitivity to IFN-γ is required for successful antigen-specific immunotherapy of a transplantable mouse tumor model for HPV-transformed tumors</atitle><jtitle>Cancer Immunology, Immunotherapy</jtitle><addtitle>Cancer Immunol Immunother</addtitle><date>2005-05-01</date><risdate>2005</risdate><volume>54</volume><issue>5</issue><spage>477</spage><epage>488</epage><pages>477-488</pages><issn>0340-7004</issn><eissn>1432-0851</eissn><coden>CIIMDN</coden><abstract>Many human tumors lose responsiveness to IFN-gamma, providing a possible mechanism for the tumor to avoid immune recognition and destruction. Here we investigate the importance of tumor responsiveness to IFN-gamma in the successful immunotherapy of TC1 tumors that were immortalized with human papillomavirus proteins E6 and E7.
To investigate the role of IFN-gamma in vivo, we constructed a variant of TC1, TC1.mugR, that is unresponsive to IFN-gamma due to overexpression of a dominant negative IFN-gamma receptor.
Using recombinant Listeria monocytogenes that express HPV-16 E7 (Lm-LLO-E7) to stimulate an antitumor response, we demonstrate that sensitivity to IFN-gamma 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-gamma 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.
Our findings identify a role for IFN-gamma in immunity to TC1 tumors and show that loss of tumor responsiveness to IFN-gamma poses a challenge to antigen-based immunotherapy.</abstract><cop>Berlin</cop><pub>Springer</pub><pmid>15750832</pmid><doi>10.1007/s00262-004-0610-0</doi><tpages>12</tpages></addata></record> |
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| subjects | Animals Antigens, Neoplasm - genetics Antigens, Neoplasm - immunology Antineoplastic agents Bacterial Vaccines - therapeutic use Biological and medical sciences Cancer Vaccines - immunology Cancer Vaccines - therapeutic use Cell Line, Tumor Cell Transformation, Viral Disease Models, Animal Female Human papillomavirus Interferon-gamma - physiology Listeria monocytogenes Listeria monocytogenes - genetics Listeria monocytogenes - immunology Lymphocytes, Tumor-Infiltrating - immunology Medical sciences Mice Mice, Inbred C57BL Neoplasm Transplantation Neoplasms, Experimental - drug therapy Neoplasms, Experimental - genetics Neoplasms, Experimental - immunology Oncogene Proteins, Viral - genetics Oncogene Proteins, Viral - immunology Original Papillomaviridae - genetics Papillomavirus E7 Proteins Papillomavirus Infections - drug therapy Papillomavirus Infections - genetics Papillomavirus Infections - immunology Pharmacology. Drug treatments Receptors, Interferon - genetics Receptors, Interferon - metabolism T-Lymphocytes, Cytotoxic - immunology Transcriptional Activation Tumor Escape - immunology Uterine Cervical Neoplasms - virology |
| title | Tumor sensitivity to IFN-γ is required for successful antigen-specific immunotherapy of a transplantable mouse tumor model for HPV-transformed tumors |
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