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

Autor: Onyshchenko K; Department of Radiation Oncology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Faculty of Biology, University of Freiburg, Freiburg, Germany.; Laboratory of Biosynthesis of Nucleic Acids, Institute of Molecular Biology and Genetics of NASU, Kyiv, Ukraine.; German Cancer Consortium (DKTK), Partner Site Freiburg, Freiburg, Germany.; German Cancer Research Center (DKFZ), Heidelberg, Germany., Luo R; Department of Radiation Oncology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Faculty of Biology, University of Freiburg, Freiburg, Germany.; German Cancer Consortium (DKTK), Partner Site Freiburg, Freiburg, Germany.; German Cancer Research Center (DKFZ), Heidelberg, Germany.; Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China., Guffart E; Department of Radiation Oncology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Faculty of Biology, University of Freiburg, Freiburg, Germany., Gaedicke S; Department of Radiation Oncology, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Grosu AL; Department of Radiation Oncology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; German Cancer Consortium (DKTK), Partner Site Freiburg, Freiburg, Germany.; German Cancer Research Center (DKFZ), Heidelberg, Germany., Firat E; Department of Radiation Oncology, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Niedermann G; Department of Radiation Oncology, Faculty of Medicine, University of Freiburg, Freiburg, Germany. gabriele.niedermann@uniklinik-freiburg.de.; German Cancer Consortium (DKTK), Partner Site Freiburg, Freiburg, Germany. gabriele.niedermann@uniklinik-freiburg.de.; German Cancer Research Center (DKFZ), Heidelberg, Germany. gabriele.niedermann@uniklinik-freiburg.de.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Apr 12; Vol. 14 (1), pp. 2087. Date of Electronic Publication: 2023 Apr 12.
DOI: 10.1038/s41467-023-37825-x
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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