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Expansion of circulating stem-like CD8(+) T cells by adding CD122-directed IL-2 complexes to radiation and anti-PD1 therapies in mice

Combination of radiation therapy (RT) with immune checkpoint blockade can enhance systemic anti-tumor T cell responses. Here, using two mouse tumor models, we demonstrate that adding long-acting CD122-directed IL-2 complexes (IL-2c) to RT/anti-PD1 further increases tumor-specific CD8(+) T cell numbe...

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Autores principales: Onyshchenko, Kateryna, Luo, Ren, Guffart, Elena, Gaedicke, Simone, Grosu, Anca-Ligia, Firat, Elke, Niedermann, Gabriele
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10097749/
https://www.ncbi.nlm.nih.gov/pubmed/37045833
http://dx.doi.org/10.1038/s41467-023-37825-x
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author Onyshchenko, Kateryna
Luo, Ren
Guffart, Elena
Gaedicke, Simone
Grosu, Anca-Ligia
Firat, Elke
Niedermann, Gabriele
author_facet Onyshchenko, Kateryna
Luo, Ren
Guffart, Elena
Gaedicke, Simone
Grosu, Anca-Ligia
Firat, Elke
Niedermann, Gabriele
author_sort Onyshchenko, Kateryna
collection PubMed
description Combination of radiation therapy (RT) with immune checkpoint blockade can enhance systemic anti-tumor T cell responses. Here, using two mouse tumor models, we demonstrate that adding long-acting CD122-directed IL-2 complexes (IL-2c) to RT/anti-PD1 further increases tumor-specific CD8(+) T cell numbers. The highest increase (>50-fold) is found in the blood circulation. Compartmental analysis of exhausted T cell subsets shows that primarily undifferentiated, stem-like, tumor-specific CD8(+) T cells expand in the blood; these cells express the chemokine receptor CXCR3, which is required for migration into tumors. In tumor tissue, effector-like but not terminally differentiated exhausted CD8(+) T cells increase. Consistent with the surge in tumor-specific CD8(+) T cells in blood that are migration and proliferation competent, we observe a CD8-dependent and CXCR3-dependent enhancement of the abscopal effect against distant/non-irradiated tumors and find that CD8(+) T cells isolated from blood after RT/anti-PD1/IL-2c triple treatment can be a rich source of tumor-specific T cells for adoptive transfers.
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spelling pubmed-100977492023-04-14 Expansion of circulating stem-like CD8(+) T cells by adding CD122-directed IL-2 complexes to radiation and anti-PD1 therapies in mice Onyshchenko, Kateryna Luo, Ren Guffart, Elena Gaedicke, Simone Grosu, Anca-Ligia Firat, Elke Niedermann, Gabriele Nat Commun Article Combination of radiation therapy (RT) with immune checkpoint blockade can enhance systemic anti-tumor T cell responses. Here, using two mouse tumor models, we demonstrate that adding long-acting CD122-directed IL-2 complexes (IL-2c) to RT/anti-PD1 further increases tumor-specific CD8(+) T cell numbers. The highest increase (>50-fold) is found in the blood circulation. Compartmental analysis of exhausted T cell subsets shows that primarily undifferentiated, stem-like, tumor-specific CD8(+) T cells expand in the blood; these cells express the chemokine receptor CXCR3, which is required for migration into tumors. In tumor tissue, effector-like but not terminally differentiated exhausted CD8(+) T cells increase. Consistent with the surge in tumor-specific CD8(+) T cells in blood that are migration and proliferation competent, we observe a CD8-dependent and CXCR3-dependent enhancement of the abscopal effect against distant/non-irradiated tumors and find that CD8(+) T cells isolated from blood after RT/anti-PD1/IL-2c triple treatment can be a rich source of tumor-specific T cells for adoptive transfers. Nature Publishing Group UK 2023-04-12 /pmc/articles/PMC10097749/ /pubmed/37045833 http://dx.doi.org/10.1038/s41467-023-37825-x 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Onyshchenko, Kateryna
Luo, Ren
Guffart, Elena
Gaedicke, Simone
Grosu, Anca-Ligia
Firat, Elke
Niedermann, Gabriele
Expansion of circulating stem-like CD8(+) T cells by adding CD122-directed IL-2 complexes to radiation and anti-PD1 therapies in mice
title Expansion of circulating stem-like CD8(+) T cells by adding CD122-directed IL-2 complexes to radiation and anti-PD1 therapies in mice
title_full Expansion of circulating stem-like CD8(+) T cells by adding CD122-directed IL-2 complexes to radiation and anti-PD1 therapies in mice
title_fullStr Expansion of circulating stem-like CD8(+) T cells by adding CD122-directed IL-2 complexes to radiation and anti-PD1 therapies in mice
title_full_unstemmed Expansion of circulating stem-like CD8(+) T cells by adding CD122-directed IL-2 complexes to radiation and anti-PD1 therapies in mice
title_short Expansion of circulating stem-like CD8(+) T cells by adding CD122-directed IL-2 complexes to radiation and anti-PD1 therapies in mice
title_sort expansion of circulating stem-like cd8(+) t cells by adding cd122-directed il-2 complexes to radiation and anti-pd1 therapies in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10097749/
https://www.ncbi.nlm.nih.gov/pubmed/37045833
http://dx.doi.org/10.1038/s41467-023-37825-x
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