Genomic Signatures of Immune Activation Predict Outcome in Advanced Stages of Ovarian Cancer and Basal-Like Breast Tumors
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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-01-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2019.01486/full |
| _version_ | 1817976827191230464 |
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| author | Ana Alcaraz-Sanabria Mariona Baliu-Piqué Cristina Saiz-Ladera Katerin Rojas Aránzazu Manzano Gloria Marquina Antonio Casado Francisco J. Cimas Pedro Pérez-Segura Atanasio Pandiella Balázs Gyorffy Balázs Gyorffy Alberto Ocana Alberto Ocana |
| author_facet | Ana Alcaraz-Sanabria Mariona Baliu-Piqué Cristina Saiz-Ladera Katerin Rojas Aránzazu Manzano Gloria Marquina Antonio Casado Francisco J. Cimas Pedro Pérez-Segura Atanasio Pandiella Balázs Gyorffy Balázs Gyorffy Alberto Ocana Alberto Ocana |
| author_sort | Ana Alcaraz-Sanabria |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T22:08:49Z |
| format | Article |
| id | doaj.art-2e80b49d6bc24d01b2d122ef6f253553 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-13T22:08:49Z |
| publishDate | 2020-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-2e80b49d6bc24d01b2d122ef6f2535532022-12-22T02:27:50ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-01-01910.3389/fonc.2019.01486506101Genomic Signatures of Immune Activation Predict Outcome in Advanced Stages of Ovarian Cancer and Basal-Like Breast TumorsAna Alcaraz-Sanabria0Mariona Baliu-Piqué1Cristina Saiz-Ladera2Katerin Rojas3Aránzazu Manzano4Gloria Marquina5Antonio Casado6Francisco J. Cimas7Pedro Pérez-Segura8Atanasio Pandiella9Balázs Gyorffy10Balázs Gyorffy11Alberto Ocana12Alberto Ocana13Translational Oncology Laboratory, Centro Regional de Investigaciones Biomedicas, Castilla-La Mancha University, Albacete, SpainExperimental Therapeutics Unit, Medical Oncology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria (IdISSC) and CIBERONC, Madrid, SpainExperimental Therapeutics Unit, Medical Oncology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria (IdISSC) and CIBERONC, Madrid, SpainExperimental Therapeutics Unit, Medical Oncology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria (IdISSC) and CIBERONC, Madrid, SpainExperimental Therapeutics Unit, Medical Oncology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria (IdISSC) and CIBERONC, Madrid, SpainExperimental Therapeutics Unit, Medical Oncology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria (IdISSC) and CIBERONC, Madrid, SpainExperimental Therapeutics Unit, Medical Oncology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria (IdISSC) and CIBERONC, Madrid, SpainTranslational Oncology Laboratory, Centro Regional de Investigaciones Biomedicas, Castilla-La Mancha University, Albacete, SpainExperimental Therapeutics Unit, Medical Oncology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria (IdISSC) and CIBERONC, Madrid, SpainInstituto de Biología Molecular y Celular del Cáncer and CIBERONC, CSIC, Salamanca, SpainDepartments of Bioinformatics and Pediatrics, Semmelweis University, Budapest, HungaryMTA TTK Lendület Cancer Biomarker Research Group, Institute of Enzymology, Budapest, HungaryTranslational Oncology Laboratory, Centro Regional de Investigaciones Biomedicas, Castilla-La Mancha University, Albacete, SpainExperimental Therapeutics Unit, Medical Oncology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria (IdISSC) and CIBERONC, Madrid, SpainThere 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.https://www.frontiersin.org/article/10.3389/fonc.2019.01486/fullovarian cancerbreast cancergenomic signaturesimmune infiltratesbiomarkers |
| spellingShingle | Ana Alcaraz-Sanabria Mariona Baliu-Piqué Cristina Saiz-Ladera Katerin Rojas Aránzazu Manzano Gloria Marquina Antonio Casado Francisco J. Cimas Pedro Pérez-Segura Atanasio Pandiella Balázs Gyorffy Balázs Gyorffy Alberto Ocana Alberto Ocana Genomic Signatures of Immune Activation Predict Outcome in Advanced Stages of Ovarian Cancer and Basal-Like Breast Tumors Frontiers in Oncology ovarian cancer breast cancer genomic signatures immune infiltrates biomarkers |
| title | Genomic Signatures of Immune Activation Predict Outcome in Advanced Stages of Ovarian Cancer and Basal-Like Breast Tumors |
| title_full | Genomic Signatures of Immune Activation Predict Outcome in Advanced Stages of Ovarian Cancer and Basal-Like Breast Tumors |
| title_fullStr | Genomic Signatures of Immune Activation Predict Outcome in Advanced Stages of Ovarian Cancer and Basal-Like Breast Tumors |
| title_full_unstemmed | Genomic Signatures of Immune Activation Predict Outcome in Advanced Stages of Ovarian Cancer and Basal-Like Breast Tumors |
| title_short | Genomic Signatures of Immune Activation Predict Outcome in Advanced Stages of Ovarian Cancer and Basal-Like Breast Tumors |
| title_sort | genomic signatures of immune activation predict outcome in advanced stages of ovarian cancer and basal like breast tumors |
| topic | ovarian cancer breast cancer genomic signatures immune infiltrates biomarkers |
| url | https://www.frontiersin.org/article/10.3389/fonc.2019.01486/full |
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