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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2018
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.
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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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