Publicaciones científicas

A therapeutically actionable pro-tumoral axis of cytokines involving interleukin-8, TNFa and IL-1B

30-jun-2022 | Revista: Cancer Discovery

Irene Olivera  1 , Rebeca Sanz-Pamplona  2 , Elixabet Bolanos  3 , Inmaculada Rodriguez  3 , Inaki Etxeberria  4 , Assunta Cirella  5 , Josune Egea  6 , Saray Garasa  7 , Itziar Migueliz  1 , Inaki Eguren-Santamaria  8 , Miguel F Sanmamed  9 , Javier Glez-Vaz  1 , Arantza Azpilikueta  5 , Maite Alvarez  10 , Maria C Ochoa  11 , Beatrice Malacrida  12 , David Propper  12 , Carlos E de Andrea  13 , Pedro Berraondo  14 , Frances R Balkwill  12 , Alvaro Teijeira  5 , Ignacio Melero  5


Abstract

Interleukin-8 (CXCL8) produced in the tumor microenvironment correlates with poor response to checkpoint inhibitors and is known to chemoattract and activate immunosuppressive myeloid leukocytes. In human cancer, IL-8 mRNA levels correlate with IL-1B and TNFa transcripts.

Both cytokines induced IL-8 functional expression from a broad variety of human cancer cell lines, primary colon-carcinoma organoids and fresh human tumor explants. Although IL-8 is absent from the mouse genome, a similar murine axis in which TNFa and IL-1B upregulate CXCL1 and CXCL2 in tumor cells was revealed.

Furthermore, intratumoral injection of TNFa and IL-1B induced IL-8 release from human malignant cells xenografted in immunodeficient mice. In all these cases, the clinically used TNFa-blockers infliximab and etanercept, or the IL-1B inhibitor anakinra were able to interfere with this pathogenic cytokine loop.

Finally, in paired plasma samples of cancer patients undergoing TNFa blockade with infliximab in a clinical-trial, reductions of circulating IL-8 were substantiated.

CITA DEL ARTÍCULO  Cancer Discov. 2022 Sep 2;12(9):2140-2157.
doi: 10.1158/2159-8290.CD-21-1115

Nuestros autores

Inmaculada Rodríguez López
Técnico de laboratorio del Programa de Inmunología e Inmunoterapia del Cima Universidad de Navarra
Josune Egea Urra
Arantza Azpilicueta Lusarreta
Maite Álvarez Rodríguez