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Unbiased chemokine receptor screening reveals similar efficacy of lymph node- and tumor-targeted T cell immunotherapy

Localization is a crucial prerequisite for immune cell function and solid tumors evade immune control by modulating immune cell infiltration into the tumor stroma. Immunosuppressive cells like regulatory T cells are attracted, while cytotoxic CD8(+) T cells are excluded. Engineering CD8(+) T cells w...

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Autores principales: Pachmayr, Ludwig O., Muehlbauer, Anton, Flommersfeld, Sophie, Graml, Franziska, Hoenninger, Julian, von Baumgarten, Louisa, Buchholz, Veit R., Grassmann, Simon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10412482/
https://www.ncbi.nlm.nih.gov/pubmed/37301772
http://dx.doi.org/10.1007/s00262-023-03472-w
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author Pachmayr, Ludwig O.
Muehlbauer, Anton
Flommersfeld, Sophie
Graml, Franziska
Hoenninger, Julian
von Baumgarten, Louisa
Buchholz, Veit R.
Grassmann, Simon
author_facet Pachmayr, Ludwig O.
Muehlbauer, Anton
Flommersfeld, Sophie
Graml, Franziska
Hoenninger, Julian
von Baumgarten, Louisa
Buchholz, Veit R.
Grassmann, Simon
author_sort Pachmayr, Ludwig O.
collection PubMed
description Localization is a crucial prerequisite for immune cell function and solid tumors evade immune control by modulating immune cell infiltration into the tumor stroma. Immunosuppressive cells like regulatory T cells are attracted, while cytotoxic CD8(+) T cells are excluded. Engineering CD8(+) T cells with chemokine receptors is a potent strategy to turn this mechanism of directed immune cell recruitment against the tumor. Here, we utilized fluorescent tagging to track the migratory behavior of tumor-specific T cells engineered with a library of all murine chemokine receptors in vivo. We then asked whether chemokine receptor-mediated redirection of antigen-specific T cells into tumors or tumor-draining lymph nodes showed superior anti-tumoral activity. We found that both targeting approaches showed higher therapeutic efficacy than control T cells. However, multiple receptors conveying the same homing pattern did not augment infiltration. Instead, in the MC38 colon carcinoma model, anti-tumoral efficacy as well as lymph node vs. tumor-homing patterns were mostly driven by CCR4 and CCR6, respectively. Overall, our data, based on fluorescent receptor tagging, identify the tumor-draining lymph node and the tumor itself as viable targets for chemokine receptor-mediated enhancement of adoptive T cell therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00262-023-03472-w.
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spelling pubmed-104124822023-08-11 Unbiased chemokine receptor screening reveals similar efficacy of lymph node- and tumor-targeted T cell immunotherapy Pachmayr, Ludwig O. Muehlbauer, Anton Flommersfeld, Sophie Graml, Franziska Hoenninger, Julian von Baumgarten, Louisa Buchholz, Veit R. Grassmann, Simon Cancer Immunol Immunother Brief Report Localization is a crucial prerequisite for immune cell function and solid tumors evade immune control by modulating immune cell infiltration into the tumor stroma. Immunosuppressive cells like regulatory T cells are attracted, while cytotoxic CD8(+) T cells are excluded. Engineering CD8(+) T cells with chemokine receptors is a potent strategy to turn this mechanism of directed immune cell recruitment against the tumor. Here, we utilized fluorescent tagging to track the migratory behavior of tumor-specific T cells engineered with a library of all murine chemokine receptors in vivo. We then asked whether chemokine receptor-mediated redirection of antigen-specific T cells into tumors or tumor-draining lymph nodes showed superior anti-tumoral activity. We found that both targeting approaches showed higher therapeutic efficacy than control T cells. However, multiple receptors conveying the same homing pattern did not augment infiltration. Instead, in the MC38 colon carcinoma model, anti-tumoral efficacy as well as lymph node vs. tumor-homing patterns were mostly driven by CCR4 and CCR6, respectively. Overall, our data, based on fluorescent receptor tagging, identify the tumor-draining lymph node and the tumor itself as viable targets for chemokine receptor-mediated enhancement of adoptive T cell therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00262-023-03472-w. Springer Berlin Heidelberg 2023-06-10 2023 /pmc/articles/PMC10412482/ /pubmed/37301772 http://dx.doi.org/10.1007/s00262-023-03472-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Brief Report
Pachmayr, Ludwig O.
Muehlbauer, Anton
Flommersfeld, Sophie
Graml, Franziska
Hoenninger, Julian
von Baumgarten, Louisa
Buchholz, Veit R.
Grassmann, Simon
Unbiased chemokine receptor screening reveals similar efficacy of lymph node- and tumor-targeted T cell immunotherapy
title Unbiased chemokine receptor screening reveals similar efficacy of lymph node- and tumor-targeted T cell immunotherapy
title_full Unbiased chemokine receptor screening reveals similar efficacy of lymph node- and tumor-targeted T cell immunotherapy
title_fullStr Unbiased chemokine receptor screening reveals similar efficacy of lymph node- and tumor-targeted T cell immunotherapy
title_full_unstemmed Unbiased chemokine receptor screening reveals similar efficacy of lymph node- and tumor-targeted T cell immunotherapy
title_short Unbiased chemokine receptor screening reveals similar efficacy of lymph node- and tumor-targeted T cell immunotherapy
title_sort unbiased chemokine receptor screening reveals similar efficacy of lymph node- and tumor-targeted t cell immunotherapy
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10412482/
https://www.ncbi.nlm.nih.gov/pubmed/37301772
http://dx.doi.org/10.1007/s00262-023-03472-w
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