Cytoreduction surgery reduces systemic myeloid suppressor cell populations and restores intratumoral immunotherapy effectiveness

BACKGROUND: Multiple immunotherapy approaches have improved adaptive anti-tumor immune responses in patients with early stage disease; however, results have been less dramatic when treating patients with late stage disease. These blunted responses are likely due to a host of factors, including chang...

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Autores principales: Predina, Jarrod D, Kapoor, Veena, Judy, Brendan F, Cheng, Guanjun, Fridlender, Zvi Gregory, Albelda, Steven M, Singhal, Sunil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3418164/
https://www.ncbi.nlm.nih.gov/pubmed/22742411
http://dx.doi.org/10.1186/1756-8722-5-34
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author Predina, Jarrod D
Kapoor, Veena
Judy, Brendan F
Cheng, Guanjun
Fridlender, Zvi Gregory
Albelda, Steven M
Singhal, Sunil
author_facet Predina, Jarrod D
Kapoor, Veena
Judy, Brendan F
Cheng, Guanjun
Fridlender, Zvi Gregory
Albelda, Steven M
Singhal, Sunil
author_sort Predina, Jarrod D
collection PubMed
description BACKGROUND: Multiple immunotherapy approaches have improved adaptive anti-tumor immune responses in patients with early stage disease; however, results have been less dramatic when treating patients with late stage disease. These blunted responses are likely due to a host of factors, including changes in the tumor microenvironment and systemic immunosuppressive features, which accompany advanced tumor states. We hypothesized that cytoreductive surgery could control these immunosuppressive networks and restore the potency of immunotherapy in advanced disease scenarios. METHODS: To test these hypotheses, two representative intratumoral immunotherapies (an adenoviral vector encoding a suicide gene, AdV-tk, or a type-I interferon, Ad.IFNα) were tested in murine models of lung cancer. Cytoreductive surgery was performed following treatment of advanced tumors. Mechanistic underpinnings were investigated using flow cytometry, in vivo leukocyte depletion methods and in vivo tumor neutralization assays. RESULTS: AdV-tk and Ad.IFNα were effective in treating early lung cancers, but had little anti-tumor effects in late stage cancers. Interestingly, in late stage scenarios, surgical cytoreduction unmasked the anti-tumor potency of both immunotherapeutic approaches. Immune mechanisms that explained restoration in anti-tumor immune responses included increased CD8 T-cell trafficking and reduced myeloid derived suppressor cell populations. CONCLUSION: This study demonstrates that surgical resection combined with immunotherapy may be a rational therapeutic option for patients with advanced stage cancer.
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spelling pubmed-34181642012-08-14 Cytoreduction surgery reduces systemic myeloid suppressor cell populations and restores intratumoral immunotherapy effectiveness Predina, Jarrod D Kapoor, Veena Judy, Brendan F Cheng, Guanjun Fridlender, Zvi Gregory Albelda, Steven M Singhal, Sunil J Hematol Oncol Research BACKGROUND: Multiple immunotherapy approaches have improved adaptive anti-tumor immune responses in patients with early stage disease; however, results have been less dramatic when treating patients with late stage disease. These blunted responses are likely due to a host of factors, including changes in the tumor microenvironment and systemic immunosuppressive features, which accompany advanced tumor states. We hypothesized that cytoreductive surgery could control these immunosuppressive networks and restore the potency of immunotherapy in advanced disease scenarios. METHODS: To test these hypotheses, two representative intratumoral immunotherapies (an adenoviral vector encoding a suicide gene, AdV-tk, or a type-I interferon, Ad.IFNα) were tested in murine models of lung cancer. Cytoreductive surgery was performed following treatment of advanced tumors. Mechanistic underpinnings were investigated using flow cytometry, in vivo leukocyte depletion methods and in vivo tumor neutralization assays. RESULTS: AdV-tk and Ad.IFNα were effective in treating early lung cancers, but had little anti-tumor effects in late stage cancers. Interestingly, in late stage scenarios, surgical cytoreduction unmasked the anti-tumor potency of both immunotherapeutic approaches. Immune mechanisms that explained restoration in anti-tumor immune responses included increased CD8 T-cell trafficking and reduced myeloid derived suppressor cell populations. CONCLUSION: This study demonstrates that surgical resection combined with immunotherapy may be a rational therapeutic option for patients with advanced stage cancer. BioMed Central 2012-06-28 /pmc/articles/PMC3418164/ /pubmed/22742411 http://dx.doi.org/10.1186/1756-8722-5-34 Text en Copyright ©2012 Predina et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Predina, Jarrod D
Kapoor, Veena
Judy, Brendan F
Cheng, Guanjun
Fridlender, Zvi Gregory
Albelda, Steven M
Singhal, Sunil
Cytoreduction surgery reduces systemic myeloid suppressor cell populations and restores intratumoral immunotherapy effectiveness
title Cytoreduction surgery reduces systemic myeloid suppressor cell populations and restores intratumoral immunotherapy effectiveness
title_full Cytoreduction surgery reduces systemic myeloid suppressor cell populations and restores intratumoral immunotherapy effectiveness
title_fullStr Cytoreduction surgery reduces systemic myeloid suppressor cell populations and restores intratumoral immunotherapy effectiveness
title_full_unstemmed Cytoreduction surgery reduces systemic myeloid suppressor cell populations and restores intratumoral immunotherapy effectiveness
title_short Cytoreduction surgery reduces systemic myeloid suppressor cell populations and restores intratumoral immunotherapy effectiveness
title_sort cytoreduction surgery reduces systemic myeloid suppressor cell populations and restores intratumoral immunotherapy effectiveness
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3418164/
https://www.ncbi.nlm.nih.gov/pubmed/22742411
http://dx.doi.org/10.1186/1756-8722-5-34
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