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@ARTICLE{RuizFernandezdeCordoba:178678,
author = {B. Ruiz-Fernandez de Cordoba and H. Moreno and K. Valencia
and N. Perurena and P. Ruedas and T. Walle$^*$ and A.
Pezonaga-Torres and J. Hinojosa and E. Guruceaga and A.
Pineda-Lucena and M. Abengozar-Muela and D. Cochonneau and
C. Zandueta and S. Martinez-Canarias and A. Teijeira and D.
Ajona and S. Ortiz-Espinosa and X. Morales and C. Ortiz de
Solorzano and M. Santisteban and L. I. Ramos-Garcia and L.
Guembe and V. Strnad and D. Heymann and S. Hervas-Stubbs and
R. Pio and M. E. Rodriguez-Ruiz and C. E. de Andrea and S.
Vicent and I. Melero and F. Lecanda and R. Martinez-Monge},
title = {{T}umor {ENPP}1({CD}203a)/{H}aptoglobin {A}xis {E}xploits
{M}yeloid-{D}erived {S}uppressor {C}ells to {P}romote
{P}ost-{R}adiotherapy {L}ocal {R}ecurrence in {B}reast
{C}ancer.},
journal = {Cancer discovery},
volume = {12},
number = {5},
issn = {2159-8274},
address = {Philadelphia, Pa.},
reportid = {DKFZ-2022-00194},
pages = {1356-1377},
year = {2022},
note = {2022 May 2;12(5):1356-1377},
abstract = {Locoregional failure (LRF) in breast cancer patients
post-surgery and post-irradiation (IR) is linked to a dismal
prognosis. In a refined new model, we identified Enpp1
(Ectonucleotide pyrophosphatase /phosphodiesterase 1/CD203a)
to be closely associated with LRF. Enpp1high circulating
tumor cells (CTC) contribute to relapse by a self-seeding
mechanism. This process requires the infiltration of
PMN-MDSC and neutrophil extracellular traps (NET) formation.
Genetic and pharmacological Enpp1 inhibition or NET blockade
extend relapse-free survival. Furthermore, in combination
with fractionated irradiation (FD), Enpp1 abrogation
obliterates LRF. Mechanistically, Enpp1-generated
adenosinergic metabolites enhance Haptoglobin (Hp)
expression. This inflammatory mediator elicits myeloid
invasiveness and promotes NET formation. Accordingly, a
significant increase in ENPP1 and NET formation is detected
in relapsed human breast cancer tumors. Moreover, high ENPP1
or HP levels are associated with poor prognosis. These
findings unveil the ENPP1/HP axis as an unanticipated
mechanism exploited by tumor cells linking inflammation to
immune remodeling favoring local relapse.},
cin = {E055},
ddc = {610},
cid = {I:(DE-He78)E055-20160331},
pnm = {315 - Bildgebung und Radioonkologie (POF4-315)},
pid = {G:(DE-HGF)POF4-315},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:35086922},
doi = {10.1158/2159-8290.CD-21-0932},
url = {https://inrepo02.dkfz.de/record/178678},
}