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@ARTICLE{Poschke:130346,
author = {I. Poschke$^*$ and M. Faryna and F. Bergmann and M.
Flossdorf$^*$ and C. Lauenstein$^*$ and J. Hermes$^*$ and U.
Hinz and T. Hank and R. Ehrenberg and M. Volkmar$^*$ and M.
Loewer and H. Glimm and T. Hackert and M. Sprick$^*$ and T.
Höfer$^*$ and A. Trumpp$^*$ and N. Halama and J. C. Hassel
and O. Strobel$^*$ and M. Büchler and U. Sahin and R.
Offringa$^*$},
title = {{I}dentification of a tumor-reactive {T}-cell repertoire in
the immune infiltrate of patients with resectable pancreatic
ductal adenocarcinoma.},
journal = {OncoImmunology},
volume = {5},
number = {12},
issn = {2162-402X},
address = {Austin, Tex.},
publisher = {Landes Bioscience},
reportid = {DKFZ-2017-05425},
pages = {e1240859 -},
year = {2016},
abstract = {The devastating prognosis of patients with resectable
pancreatic ductal adenocarcinoma (PDA) presents an urgent
need for the development of therapeutic strategies targeting
disseminated tumor cells. Until now, T-cell therapy has been
scarcely pursued in PDA, due to the prevailing view that it
represents a poorly immunogenic tumor.We systematically
analyzed T-cell infiltrates in tumor biopsies from 127
patients with resectable PDA by means of
immunohistochemistry, flow cytometry, T-cell receptor (TCR)
deep-sequencing and functional analysis of in vitro expanded
T-cell cultures. Parallel studies were performed on
tumor-infiltrating lymphocytes (TIL) from 44 patients with
metastatic melanoma.Prominent T-cell infiltrates, as well as
tertiary lymphoid structures harboring proliferating
T-cells, were detected in the vast majority of biopsies from
PDA patients. The notion that the tumor is a site of local
T-cell expansion was strengthened by TCR deep-sequencing,
revealing that the T-cell repertoire in the tumor is
dominated by highly frequent CDR3 sequences that can be up
to 10,000-fold enriched in tumor as compared to peripheral
blood. In fact, TCR repertoire composition in PDA resembled
that in melanoma. Moreover, in vitro expansion of TILs was
equally efficient for PDA and melanoma, resulting in T-cell
cultures displaying HLA class I-restricted reactivity
against autologous tumor cells.The tumor-infiltrating T-cell
response in PDA shows striking similarity to that in
melanoma, where adoptive T-cell therapy has significant
therapeutic impact. Our findings indicate that T-cell-based
therapies may be used to counter disease recurrence in
patients with resectable PDA.},
cin = {G180 / B086},
ddc = {610},
cid = {I:(DE-He78)G180-20160331 / I:(DE-He78)B086-20160331},
pnm = {317 - Translational cancer research (POF3-317)},
pid = {G:(DE-HGF)POF3-317},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:28123878},
pmc = {pmc:PMC5215250},
doi = {10.1080/2162402X.2016.1240859},
url = {https://inrepo02.dkfz.de/record/130346},
}