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@ARTICLE{Goswami:148826,
author = {S. Goswami and T. Walle$^*$ and A. E. Cornish and S. Basu
and S. Anandhan and I. Fernandez and L. Vence and J. Blando
and H. Zhao and S. S. Yadav and M. Ott and L. Y. Kong and A.
B. Heimberger and J. de Groot and B. Sepesi and M. Overman
and S. Kopetz and J. P. Allison and D. Pe'er and P. Sharma},
title = {{I}mmune profiling of human tumors identifies {CD}73 as a
combinatorial target in glioblastoma.},
journal = {Nature medicine},
volume = {26},
number = {1},
issn = {1546-170X},
address = {New York, NY},
publisher = {Nature America Inc.},
reportid = {DKFZ-2020-00018},
pages = {39-46},
year = {2020},
note = {26 (1), 39-46Jan 2020 / #EA:E055#},
abstract = {Immune checkpoint therapy with anti-CTLA-4 and
anti-PD-1/PD-L1 has revolutionized the treatment of many
solid tumors. However, the clinical efficacy of immune
checkpoint therapy is limited to a subset of patients with
specific tumor types1,2. Multiple clinical trials with
combinatorial immune checkpoint strategies are ongoing;
however, the mechanistic rationale for tumor-specific
targeting of immune checkpoints is elusive. To garner an
insight into tumor-specific immunomodulatory targets, we
analyzed 94 patients representing five different cancer
types, including those that respond relatively well to
immune checkpoint therapy and those that do not, such as
glioblastoma multiforme, prostate cancer and colorectal
cancer. Through mass cytometry and single-cell RNA
sequencing, we identified a unique population of CD73hi
macrophages in glioblastoma multiforme that persists after
anti-PD-1 treatment. To test if targeting CD73 would be
important for a successful combination strategy in
glioblastoma multiforme, we performed reverse translational
studies using CD73-/- mice. We found that the absence of
CD73 improved survival in a murine model of glioblastoma
multiforme treated with anti-CTLA-4 and anti-PD-1. Our data
identified CD73 as a specific immunotherapeutic target to
improve antitumor immune responses to immune checkpoint
therapy in glioblastoma multiforme and demonstrate that
comprehensive human and reverse translational studies can be
used for rational design of combinatorial immune checkpoint
strategies.},
cin = {E055},
ddc = {610},
cid = {I:(DE-He78)E055-20160331},
pnm = {315 - Imaging and radiooncology (POF3-315)},
pid = {G:(DE-HGF)POF3-315},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:31873309},
doi = {10.1038/s41591-019-0694-x},
url = {https://inrepo02.dkfz.de/record/148826},
}