TY  - JOUR
AU  - Onyshchenko, Kateryna
AU  - Luo, Ren
AU  - Guffart, Elena
AU  - Gaedicke, Simone
AU  - Grosu, Anca-Ligia
AU  - Firat, Elke
AU  - Niedermann, Gabriele
TI  - Expansion of circulating stem-like CD8+ T cells by adding CD122-directed IL-2 complexes to radiation and anti-PD1 therapies in mice.
JO  - Nature Communications
VL  - 14
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DKFZ-2023-00739
SP  - 2087
PY  - 2023
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:37045833
DO  - DOI:10.1038/s41467-023-37825-x
UR  - https://inrepo02.dkfz.de/record/275373
ER  -