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@ARTICLE{Onyshchenko:275373,
author = {K. Onyshchenko$^*$ and R. Luo$^*$ and E. Guffart and S.
Gaedicke and A.-L. Grosu$^*$ and E. Firat and G.
Niedermann$^*$},
title = {{E}xpansion of circulating stem-like {CD}8+ {T} cells by
adding {CD}122-directed {IL}-2 complexes to radiation and
anti-{PD}1 therapies in mice.},
journal = {Nature Communications},
volume = {14},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DKFZ-2023-00739},
pages = {2087},
year = {2023},
abstract = {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.},
cin = {FR01},
ddc = {500},
cid = {I:(DE-He78)FR01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37045833},
doi = {10.1038/s41467-023-37825-x},
url = {https://inrepo02.dkfz.de/record/275373},
}