Journal Article

DKFZ-2022-00194

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Tumor ENPP1(CD203a)/Haptoglobin Axis Exploits Myeloid-Derived Suppressor Cells to Promote Post-Radiotherapy Local Recurrence in Breast Cancer.

Ruiz-Fernandez de Cordoba, B. ; Moreno, H. ; Valencia, K. ; Perurena, N. ; Ruedas, P. ; Walle, T.DKFZ* ; Pezonaga-Torres, A. ; Hinojosa, J. ; Guruceaga, E. ; Pineda-Lucena, A. ; Abengozar-Muela, M. ; Cochonneau, D. ; Zandueta, C. ; Martinez-Canarias, S. ; Teijeira, A. ; Ajona, D. ; Ortiz-Espinosa, S. ; Morales, X. ; Ortiz de Solorzano, C. ; Santisteban, M. ; Ramos-Garcia, L. I. ; Guembe, L. ; Strnad, V. ; Heymann, D. ; Hervas-Stubbs, S. ; Pio, R. ; Rodriguez-Ruiz, M. E. ; de Andrea, C. E. ; Vicent, S. ; Melero, I. ; Lecanda, F. ; Martinez-Monge, R.

2022
Philadelphia, Pa.

This record in other databases:  

Please use a persistent id in citations: doi:10.1158/2159-8290.CD-21-0932

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.

Note: 2022 May 2;12(5):1356-1377

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Contributing Institute(s):

1. E055 KKE Translationale Radioonkologie (E055)

Research Program(s):

1. 315 - Bildgebung und Radioonkologie (POF4-315) (POF4-315)

Appears in the scientific report 2022

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Essential Science Indicators ; IF >= 30 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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