Abstract 91P
Background
Integrins, transmembrane receptors that mediate cell-extracellular matrix and cell-cell interaction, have been linked to cancer features. A less explored function of integrins in cancer is their role in leukocyte homing and activation. Understanding their role and relationship with immune infiltrates and immune checkpoints is an area of interest in cancer research.
Methods
The gene expression of 34 different integrins was explored in relation with breast cancer patient outcome using transcriptomic data (Affymetrix dataset, exploratory cohort) and the METABRIC study (validation cohort). The TIMER online tool was used to explore the association of the identified integrins and immune infiltration, and the TCGA and METABRIC studies to analyze the correlation between integrin expression and genomic signatures of immune activation.
Results
We identified 7 individual genes which encode for integrin α and β subunits, ITGA4, ITGB2, ITGAX, ITGB7, ITGAM, ITGAL and ITGA8, which predict favorable prognosis in Basal-like and HER2+ breast cancer. Their expression positively correlated with the presence of immune infiltrates within the tumor (dendritic cells, CD4+ T cells, neutrophils, CD8+ T cells and B cells), with markers of T cell activation and antigen presentation, and with gene signatures of immune surveillance (cytotoxic T lymphocyte activation and IFN gamma signature). By contrast those integrins which predicted for detrimental outcome (IBSP, ITGB3BP, ITGB6, ITGB1 and ITGAV) were not associated with any of these parameters.
Conclusions
Our analysis identifies an integrin signature composed of 7 genes with potential to recognize immune infiltrated and activated Basal-like and HER2+ breast cancers with favorable prognosis.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
This work has been supported by Instituto de Salud Carlos III (PI19/00808), ACEPAIN, Diputación de Albacete, CIBERONC and CRIS Cancer Foundation.
Disclosure
P. Pérez Segura: Research grant/Funding (self), Research grant/Funding (institution): Merck and MSD. A. Pandiella: Advisory/Consultancy: Daiichi Sankyo. A. Ocaña: Research grant/Funding (self), Research grant/Funding (institution): Entrechem; Travel/Accommodation/Expenses: Merck; Advisory/Consultancy: Daiichi Sankyo. All other authors have declared no conflicts of interest.