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IL-33 delays metastatic peritoneal cancer progression inducing an allergic microenvironment
Ovarian cancer is frequently diagnosed as peritoneal carcinomatosis. Unlike other tumor locations, the peritoneal cavity is commonly exposed to gut-breaching and ascending genital microorganisms and has a unique immune environment. IL-33 is a local cytokine that can activate innate and adaptive immu...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287802/ https://www.ncbi.nlm.nih.gov/pubmed/30546956 http://dx.doi.org/10.1080/2162402X.2018.1515058 |
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author | Perales-Puchalt, Alfredo Svoronos, Nikolaos Villarreal, Daniel O. Zankharia, Urvi Reuschel, Emma Wojtak, Krzysztof Payne, Kyle K. Duperret, Elizabeth K. Muthumani, Kar Conejo-Garcia, Jose R. Weiner, David B. |
author_facet | Perales-Puchalt, Alfredo Svoronos, Nikolaos Villarreal, Daniel O. Zankharia, Urvi Reuschel, Emma Wojtak, Krzysztof Payne, Kyle K. Duperret, Elizabeth K. Muthumani, Kar Conejo-Garcia, Jose R. Weiner, David B. |
author_sort | Perales-Puchalt, Alfredo |
collection | PubMed |
description | Ovarian cancer is frequently diagnosed as peritoneal carcinomatosis. Unlike other tumor locations, the peritoneal cavity is commonly exposed to gut-breaching and ascending genital microorganisms and has a unique immune environment. IL-33 is a local cytokine that can activate innate and adaptive immunity. We studied the effectiveness of local IL-33 delivery in the treatment of cancer that has metastasized to the peritoneal cavity. Direct peritoneal administration of IL-33 delayed the progression of metastatic peritoneal cancer. Prolongation in survival was not associated with a direct effect of IL-33 on tumor cells, but with major changes in the immune microenvironment of the tumor. IL-33 promoted a significant increase in the leukocyte compartment of the tumor immunoenvironment and an allergic cytokine profile. We observed a substantial increase in the number of activated CD4(+) T-cells accompanied by peritoneal eosinophil infiltration, B-cell activation and activation of peritoneal macrophages which displayed tumoricidal capacity. Depletion of CD4(+) cells, eosinophils or macrophages reduced the anti-tumor effects of IL-33 but none of these alone were sufficient to completely abrogate its positive benefit. In conclusion, local administration of IL-33 generates an allergic tumor environment resulting in a novel approach for treatment of metastatic peritoneal malignancies, such as advanced ovarian cancer. |
format | Online Article Text |
id | pubmed-6287802 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-62878022018-12-13 IL-33 delays metastatic peritoneal cancer progression inducing an allergic microenvironment Perales-Puchalt, Alfredo Svoronos, Nikolaos Villarreal, Daniel O. Zankharia, Urvi Reuschel, Emma Wojtak, Krzysztof Payne, Kyle K. Duperret, Elizabeth K. Muthumani, Kar Conejo-Garcia, Jose R. Weiner, David B. Oncoimmunology Original Research Ovarian cancer is frequently diagnosed as peritoneal carcinomatosis. Unlike other tumor locations, the peritoneal cavity is commonly exposed to gut-breaching and ascending genital microorganisms and has a unique immune environment. IL-33 is a local cytokine that can activate innate and adaptive immunity. We studied the effectiveness of local IL-33 delivery in the treatment of cancer that has metastasized to the peritoneal cavity. Direct peritoneal administration of IL-33 delayed the progression of metastatic peritoneal cancer. Prolongation in survival was not associated with a direct effect of IL-33 on tumor cells, but with major changes in the immune microenvironment of the tumor. IL-33 promoted a significant increase in the leukocyte compartment of the tumor immunoenvironment and an allergic cytokine profile. We observed a substantial increase in the number of activated CD4(+) T-cells accompanied by peritoneal eosinophil infiltration, B-cell activation and activation of peritoneal macrophages which displayed tumoricidal capacity. Depletion of CD4(+) cells, eosinophils or macrophages reduced the anti-tumor effects of IL-33 but none of these alone were sufficient to completely abrogate its positive benefit. In conclusion, local administration of IL-33 generates an allergic tumor environment resulting in a novel approach for treatment of metastatic peritoneal malignancies, such as advanced ovarian cancer. Taylor & Francis 2018-09-06 /pmc/articles/PMC6287802/ /pubmed/30546956 http://dx.doi.org/10.1080/2162402X.2018.1515058 Text en © 2019 The Author(s). Published with license by Taylor & Francis Group, LLC http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. |
spellingShingle | Original Research Perales-Puchalt, Alfredo Svoronos, Nikolaos Villarreal, Daniel O. Zankharia, Urvi Reuschel, Emma Wojtak, Krzysztof Payne, Kyle K. Duperret, Elizabeth K. Muthumani, Kar Conejo-Garcia, Jose R. Weiner, David B. IL-33 delays metastatic peritoneal cancer progression inducing an allergic microenvironment |
title | IL-33 delays metastatic peritoneal cancer progression inducing an allergic microenvironment |
title_full | IL-33 delays metastatic peritoneal cancer progression inducing an allergic microenvironment |
title_fullStr | IL-33 delays metastatic peritoneal cancer progression inducing an allergic microenvironment |
title_full_unstemmed | IL-33 delays metastatic peritoneal cancer progression inducing an allergic microenvironment |
title_short | IL-33 delays metastatic peritoneal cancer progression inducing an allergic microenvironment |
title_sort | il-33 delays metastatic peritoneal cancer progression inducing an allergic microenvironment |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287802/ https://www.ncbi.nlm.nih.gov/pubmed/30546956 http://dx.doi.org/10.1080/2162402X.2018.1515058 |
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