Title
Genomic Signatures of Immune Activation Predict Outcome in Advanced Stages of Ovarian Cancer and Basal-Like Breast Tumors
Date Issued
10 January 2020
Access level
open access
Resource Type
journal article
Author(s)
Alcaraz-Sanabria A.
Baliu-Piqué M.
Saiz-Ladera C.
Manzano A.
Marquina G.
Casado A.
Cimas F.J.
Pérez-Segura P.
Pandiella A.
Gyorffy B.
Ocana A.
Instituto de Investigación Sanitaria (IdISSC)
Publisher(s)
Frontiers Media S.A.
Abstract
There is an unmet need for new therapies in metastatic ovarian cancer and basal-like breast cancer since no curative therapies are currently available. Immunotherapy has shown to be active in several solid tumors, but particularly more in those where a pre-activated immune state does exist. In this work, we aim to identify biomarkers that could distinguish immune-activated tumors and predict response to therapies in ovarian and basal-like breast cancer, as well as their association with the level of tumor immune infiltration. We found that the combined expression of IFNG, CD30, CXCL13, and PRF1 correlated with better overall survival (OS) in advanced stage ovarian cancer. This was confirmed using an independent dataset from TCGA. Interestingly, we observed that this gene combination also predicted for better prognosis in ovarian tumors with low mutational load, which typically respond less to immunotherapy. Expression of IFNG, CD30, CXCL13, and PRF1 was associated with increased level of immune infiltrates (CD8+ T cells, dendritic cells, and neutrophils) within the tumor. Moreover, we found that these gene signature also correlated with an increased OS and with a higher level of tumor immune infiltrates (B cells, CD8+ T cells, CD4+ T cells, neutrophils, and dendritic cells) in basal-like breast cancer. In conclusion, our analysis identifies genes signatures with potential to recognize immune activated ovarian and basal-like breast cancers with favorable prognosis and with a remarkable predictive capacity in tumors with low mutational burden. The presented results led to a hypothesis being formulated, but prospective clinical studies are needed to support a potential clinical application.
Volume
9
Language
English
OCDE Knowledge area
Oncología
Subjects
Scopus EID
2-s2.0-85078216890
Source
Frontiers in Oncology
ISSN of the container
2234943X
Sponsor(s)
Funding. This work has been supported by Instituto de Salud Carlos III (PI16/01121 and PI19/00808), ACEPAIN; Diputación de Albacete, CIBERONC and CRIS Cancer Foundation (to AO). Ministry of Economy and Competitiveness of Spain (BFU2015-71371-R), the Instituto de Salud Carlos III through the Spanish Cancer Centers Network Program (RD12/0036/0003) and CIBERONC, the scientific foundation of the AECC and the CRIS Foundation (to AP). The work carried out in our laboratories receive support from the European Community through the regional development funding program (FEDER).
Sources of information:
Directorio de Producción Científica
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