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@ARTICLE{Meng:285421,
author = {Z. Meng$^*$ and A. Rodriguez Ehrenfried$^*$ and C. L.
Tan$^*$ and L. K. Steffens$^*$ and H. Kehm$^*$ and S.
Zens$^*$ and C. Lauenstein$^*$ and A. Paul$^*$ and M.
Schwab$^*$ and J. Förster$^*$ and M. Salek$^*$ and A.
Riemer$^*$ and H. Wu and C. Eckert and C.-S. Leonhardt and
O. Strobel and M. Volkmar$^*$ and I. Poschke$^*$ and R.
Offringa$^*$},
title = {{T}ranscriptome-based identification of tumor-reactive and
bystander {CD}8+ {T} cell receptor clonotypes in human
pancreatic cancer.},
journal = {Science translational medicine},
volume = {15},
number = {722},
issn = {1946-6234},
address = {Washington, DC},
publisher = {AAAS},
reportid = {DKFZ-2023-02366},
pages = {eadh9562},
year = {2023},
note = {#EA:D200#EA:D170#LA:D200#LA:D170# / HI-TRON},
abstract = {Pancreatic ductal adenocarcinoma (PDAC) is generally
refractory to immune checkpoint blockade, although patients
with genetically unstable tumors can show modest therapeutic
benefit. We previously demonstrated the presence of
tumor-reactive CD8+ T cells in PDAC samples. Here, we
charted the tumor-infiltrating T cell repertoire in PDAC by
combining single-cell transcriptomics with functional
testing of T cell receptors (TCRs) for reactivity against
autologous tumor cells. On the basis of a comprehensive
dataset including 93 tumor-reactive and 65 bystander TCR
clonotypes, we delineated a gene signature that effectively
distinguishes between these T cell subsets in PDAC, as well
as in other tumor indications. This revealed a high
frequency of tumor-reactive TCR clonotypes in three
genetically unstable samples. In contrast, the T cell
repertoire in six genetically stable PDAC tumors was largely
dominated by bystander T cells. Nevertheless, multiple
tumor-reactive TCRs were successfully identified in each of
these samples, thereby providing a perspective for
personalized immunotherapy in this treatment-resistant
indication.},
cin = {D200 / D190 / D170 / F130},
ddc = {500},
cid = {I:(DE-He78)D200-20160331 / I:(DE-He78)D190-20160331 /
I:(DE-He78)D170-20160331 / I:(DE-He78)F130-20160331},
pnm = {314 - Immunologie und Krebs (POF4-314)},
pid = {G:(DE-HGF)POF4-314},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37967201},
doi = {10.1126/scitranslmed.adh9562},
url = {https://inrepo02.dkfz.de/record/285421},
}