Publicaciones científicas

Tumor ENPP1(CD203a)/Haptoglobin Axis Exploits Myeloid-Derived Suppressor Cells to Promote Post-Radiotherapy Local Recurrence in Breast Cancer

27-ene-2022 | Revista: Cancer Discovery

Borja Ruiz-Fernandez de Cordoba  1 , Haritz Moreno  2 , Karmele Valencia  3 , Naiara Perurena  4 , Pablo Ruedas  1 , Thomas Walle  5 , Alberto Pezonaga-Torres  1 , Juan Hinojosa  1 , Elisabet Guruceaga  6 , Antonio Pineda-Lucena  7 , Marta Abengozar-Muela  8 , Denis Cochonneau  9 , Carolina Zandueta  10 , Susana Martinez-Canarias  1 , Alvaro Teijeira  11 , Daniel Ajona  12 , Sergio Ortiz-Espinosa  2 , Xabier Morales  13 , Carlos Ortiz de Solorzano  14 , Marta Santisteban  15 , Luis I Ramos-Garcia  16 , Laura Guembe  17 , Vratislav Strnad  18 , Dominique Heymann  19 , Sandra Hervas-Stubbs  20 , Ruben Pio  21 , Maria E Rodriguez-Ruiz  22 , Carlos E de Andrea  23 , Silvestre Vicent  24 , Ignacio Melero  11 , Fernando Lecanda  25 , Rafael Martinez-Monge  26


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.

CITA DEL ARTÍCULO  Cancer Discov.  2022 Jan 27;candisc.0932.2021.  doi: 10.1158/2159-8290.CD-21-0932.

Nuestros autores

Borja Ruiz Fernández de Córdoba
Haritz Moreno Moreno
Elizabet Guruceaga Martínez
Técnico de Investigación Bioinformático Plataforma Bioinformática
Carolina Zandueta Pascual
Álvaro Teijeira Sánchez
Xabier Morales Urteaga
Técnico de Investigación Plataforma de Imagen
Laura Guembe Echarri
Colaborador de Investigación Plataforma de Morfología
Sandra Hervás Stubbs
Investigadora | Investigadora principal Programa de Investigación de Inmunología e Inmunoterapia
Silvestre Vicent Cambra