TY  - JOUR
AU  - Ruiz-Fernandez de Cordoba, Borja
AU  - Moreno, Haritz
AU  - Valencia, Karmele
AU  - Perurena, Naiara
AU  - Ruedas, Pablo
AU  - Walle, Thomas
AU  - Pezonaga-Torres, Alberto
AU  - Hinojosa, Juan
AU  - Guruceaga, Elisabet
AU  - Pineda-Lucena, Antonio
AU  - Abengozar-Muela, Marta
AU  - Cochonneau, Denis
AU  - Zandueta, Carolina
AU  - Martinez-Canarias, Susana
AU  - Teijeira, Alvaro
AU  - Ajona, Daniel
AU  - Ortiz-Espinosa, Sergio
AU  - Morales, Xabier
AU  - Ortiz de Solorzano, Carlos
AU  - Santisteban, Marta
AU  - Ramos-Garcia, Luis I
AU  - Guembe, Laura
AU  - Strnad, Vratislav
AU  - Heymann, Dominique
AU  - Hervas-Stubbs, Sandra
AU  - Pio, Ruben
AU  - Rodriguez-Ruiz, Maria E
AU  - de Andrea, Carlos E
AU  - Vicent, Silvestre
AU  - Melero, Ignacio
AU  - Lecanda, Fernando
AU  - Martinez-Monge, Rafael
TI  - Tumor ENPP1(CD203a)/Haptoglobin Axis Exploits Myeloid-Derived Suppressor Cells to Promote Post-Radiotherapy Local Recurrence in Breast Cancer.
JO  - Cancer discovery
VL  - 12
IS  - 5
SN  - 2159-8274
CY  - Philadelphia, Pa.
M1  - DKFZ-2022-00194
SP  - 1356-1377
PY  - 2022
N1  - 2022 May 2;12(5):1356-1377
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:35086922
DO  - DOI:10.1158/2159-8290.CD-21-0932
UR  - https://inrepo02.dkfz.de/record/178678
ER  -