Unbiased chemokine receptor screening reveals similar efficacy of lymph node- and tumor-targeted T cell immunotherapy
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Published:2023-06-10
Issue:9
Volume:72
Page:3111-3124
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ISSN:0340-7004
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Container-title:Cancer Immunology, Immunotherapy
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language:en
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Short-container-title:Cancer Immunol Immunother
Author:
Pachmayr Ludwig O., Muehlbauer Anton, Flommersfeld Sophie, Graml Franziska, Hoenninger Julian, von Baumgarten Louisa, Buchholz Veit R.ORCID, Grassmann SimonORCID
Abstract
AbstractLocalization 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.
Funder
Deutsche Forschungsgemeinschaft Deutsche Krebshilfe Technische Universität München
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology,Immunology,Immunology and Allergy
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