Serial transplantation unmasks galectin-9 contribution to tumor immune escape in the MB49 murine model
Abstract Mechanisms of tumor immune escape are quite diverse and require specific approaches for their exploration in syngeneic tumor models. In several human malignancies, galectin-9 (gal-9) is suspected to contribute to the immune escape. However, in contrast with what has been done for the infilt...
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doaj-f1c73674a7d746609c3611d3bc2df3af2021-03-11T12:19:48ZengNature Publishing GroupScientific Reports2045-23222021-03-0111111810.1038/s41598-021-84270-1Serial transplantation unmasks galectin-9 contribution to tumor immune escape in the MB49 murine modelValentin Baloche0Julie Rivière1Thi Bao Tram Tran2Aurore Gelin3Olivia Bawa4Nicolas Signolle5M′Boyba Khadija Diop6Philippe Dessen7Stéphanie Beq8Muriel David9Pierre Busson10CNRS, UMR 9018, Gustave Roussy and Université Paris-SaclayInserm, U1170, Gustave RoussyCNRS, UMR 9018, Gustave Roussy and Université Paris-SaclayCNRS, UMR 9018, Gustave Roussy and Université Paris-SaclayPlateforme de pathologie expérimentale et translationnelle, UMS AMMICA, Gustave RoussyPlateforme de pathologie expérimentale et translationnelle, UMS AMMICA, Gustave RoussyPlateforme de Bioinformatique, UMS AMMICA, Gustave RoussyPlateforme de Bioinformatique, UMS AMMICA, Gustave RoussyHiFiBiO Therapeutics, Pépinière Paris Santé CochinHiFiBiO Therapeutics, Pépinière Paris Santé CochinCNRS, UMR 9018, Gustave Roussy and Université Paris-SaclayAbstract Mechanisms of tumor immune escape are quite diverse and require specific approaches for their exploration in syngeneic tumor models. In several human malignancies, galectin-9 (gal-9) is suspected to contribute to the immune escape. However, in contrast with what has been done for the infiltrating cells, the contribution of gal-9 produced by malignant cells has never been demonstrated in an animal model. Therefore, we derived isogenic clones—either positive or negative for gal-9—from the MB49 murine bladder carcinoma cell line. A progressive and consistent reduction of tumor growth was observed when gal-9-KO cells were subjected to serial transplantations into syngeneic mice. In contrast, tumor growth was unaffected during parallel serial transplantations into nude mice, thus linking tumor inhibition to the enhancement of the immune response against gal-9-KO tumors. This stronger immune response was at least in part explained by changing patterns of response to interferon-γ. One consistent change was a more abundant production of CXCL10, a major inflammatory factor whose production is often induced by interferon-γ. Overall, these observations demonstrate for the first time that serial transplantation into syngeneic mice can be a valuable experimental approach for the exploration of novel mechanisms of tumor immune escape.https://doi.org/10.1038/s41598-021-84270-1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Valentin Baloche Julie Rivière Thi Bao Tram Tran Aurore Gelin Olivia Bawa Nicolas Signolle M′Boyba Khadija Diop Philippe Dessen Stéphanie Beq Muriel David Pierre Busson |
spellingShingle |
Valentin Baloche Julie Rivière Thi Bao Tram Tran Aurore Gelin Olivia Bawa Nicolas Signolle M′Boyba Khadija Diop Philippe Dessen Stéphanie Beq Muriel David Pierre Busson Serial transplantation unmasks galectin-9 contribution to tumor immune escape in the MB49 murine model Scientific Reports |
author_facet |
Valentin Baloche Julie Rivière Thi Bao Tram Tran Aurore Gelin Olivia Bawa Nicolas Signolle M′Boyba Khadija Diop Philippe Dessen Stéphanie Beq Muriel David Pierre Busson |
author_sort |
Valentin Baloche |
title |
Serial transplantation unmasks galectin-9 contribution to tumor immune escape in the MB49 murine model |
title_short |
Serial transplantation unmasks galectin-9 contribution to tumor immune escape in the MB49 murine model |
title_full |
Serial transplantation unmasks galectin-9 contribution to tumor immune escape in the MB49 murine model |
title_fullStr |
Serial transplantation unmasks galectin-9 contribution to tumor immune escape in the MB49 murine model |
title_full_unstemmed |
Serial transplantation unmasks galectin-9 contribution to tumor immune escape in the MB49 murine model |
title_sort |
serial transplantation unmasks galectin-9 contribution to tumor immune escape in the mb49 murine model |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-03-01 |
description |
Abstract Mechanisms of tumor immune escape are quite diverse and require specific approaches for their exploration in syngeneic tumor models. In several human malignancies, galectin-9 (gal-9) is suspected to contribute to the immune escape. However, in contrast with what has been done for the infiltrating cells, the contribution of gal-9 produced by malignant cells has never been demonstrated in an animal model. Therefore, we derived isogenic clones—either positive or negative for gal-9—from the MB49 murine bladder carcinoma cell line. A progressive and consistent reduction of tumor growth was observed when gal-9-KO cells were subjected to serial transplantations into syngeneic mice. In contrast, tumor growth was unaffected during parallel serial transplantations into nude mice, thus linking tumor inhibition to the enhancement of the immune response against gal-9-KO tumors. This stronger immune response was at least in part explained by changing patterns of response to interferon-γ. One consistent change was a more abundant production of CXCL10, a major inflammatory factor whose production is often induced by interferon-γ. Overall, these observations demonstrate for the first time that serial transplantation into syngeneic mice can be a valuable experimental approach for the exploration of novel mechanisms of tumor immune escape. |
url |
https://doi.org/10.1038/s41598-021-84270-1 |
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