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01-12-2021 | Vaccination | Original Article

Human hydatid cyst fluid-induced therapeutic anti-cancer immune responses via NK1.1⁺ cell activation in mice

Authors: Edgardo Berriel, Teresa Freire, Carolina Chiale, Ernesto Rodríguez, Gabriel Morón, Gabriel Fernández-Graña, Martina Crispo, Nora Berois, Eduardo Osinaga

Published in: Cancer Immunology, Immunotherapy | Issue 12/2021

Abstract

Echinococcus granulosus is a cestode parasite which causes cystic echinococcosis disease. Previously we observed that vaccination with E. granulosus antigens from human hydatid cyst fluid (HCF) significantly inhibits colon cancer growth. In the present work, we evaluate the anti-tumor immune response induced by human HCF against LL/2 lung cancer in mice. HCF vaccination protected from tumor growth, both in prophylactic and therapeutic settings, and significantly increased mouse survival compared to control mice. Considering that tumor-associated carbohydrate antigens are expressed in E. granulosus, we oxidized terminal carbohydrates in HCF with sodium periodate. This treatment abrogates the anti-tumor activity induced by HCF vaccination. We found that HCF vaccination-induced IgG antibodies that recognize LL/2 tumor cells by flow cytometry. An antigen-specific immune response is induced with HCF vaccination in the tumor-draining lymph nodes and spleen characterized by the production of IL-5 and, in less extent, IFNɣ. In the tumor microenvironment, we found that NK1.1 positive cells from HCF-treated mice showed higher expression of CD69 than control mice ones, indicating a higher level of activation. When we depleted these cells by administrating the NK-specific antibody NK1.1, a significantly decreased survival was observed in HCF-induced mice, suggesting that NK1.1⁺ cells mediate the anti-tumor protection induced by HCF. These results suggest that HCF can evoke an integrated anti-tumor immune response involving both, the innate and adaptive components, and provide novel insights into the understanding of the intricate relationship between HCF vaccination and tumor growth.

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Title: Human hydatid cyst fluid-induced therapeutic anti-cancer immune responses via NK1.1+ cell activation in mice
Authors: Edgardo Berriel
Teresa Freire
Carolina Chiale
Ernesto Rodríguez
Gabriel Morón
Gabriel Fernández-Graña
Martina Crispo
Nora Berois
Eduardo Osinaga
Publication date: 01-12-2021
Publisher: Springer Berlin Heidelberg
Keyword: Vaccination
Published in: Cancer Immunology, Immunotherapy / Issue 12/2021
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-021-02948-x

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