Expression of MHC class I, HLA-A and HLA-B identifies immune-activated breast tumors with favorable outcome
| Autor: | Alberto Ocaña, Sara Morcillo García, Cristina Nieto-Jiménez, Fernando Andrés-Pretel, Eitan Amir, Balázs Győrffy, Miriam Nuncia-Cantarero, Javier Pérez-Peña, María Del Mar Noblejas-López, Eva María Galán-Moya, Atanasio Pandiella |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
lcsh:Immunologic diseases. Allergy T cell mhc-i Immunology lcsh:RC254-282 GZMB 03 medical and health sciences 0302 clinical medicine Breast cancer Immune system hla-a breast cancer hla-b MHC class I Gene expression medicine Immunology and Allergy Original Research biology basal-like breast medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens HLA-B HLA-A immune ractivated 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis biology.protein Cancer research lcsh:RC581-607 |
| Zdroj: | OncoImmunology, Vol 8, Iss 10 (2019) Oncoimmunology |
| Popis: | Antigen recognition by MHC class I molecules is a key step for the initiation of the immune response. We hypothesized that expression of these molecules could be a marker of immune-activated breast cancers. Data from KM Plotter were extracted to develop an exploratory cohort. Information from Cancer Genome Atlas (TCGA) and METABRIC was used to create two validation cohorts. Raw data were re-processed and analyzed using plyr R and Bioconductor. We predicted epitope-HLA binding to MHC I molecules by using NetMHC 4.0. Cox proportional hazards regression was computed to correlate gene expression and survival outcome. There was a weak but positive correlation between mutational burden and the expression of most MHC class I molecules. In the exploratory cohort, expression of HLA-A and HLA-B was associated with favorable relapse-free survival (RFS) and overall survival (OS) in the basal-like subgroup. This was confirmed in the METABRIC and TCGA dataset. Expression of HLA-A and HLA-B was associated with biomarkers of T cell activation (GZMA, GZMB, and PRF1) and improved the predictive capacity of known immunologic signatures. Several neopeptides expressed in breast cancer were also identified including FUK, SNAPC3, GC, ANO8, DOT1L, HIST1H3F, MYBPH, STX2, FRMD6, CPSF1, or SMTN, among others. Expression of HLA A and B is associated with T cell activation and identifies immune activated, basal-like breast cancers with favorable prognosis. Antigen recognition markers should be incorporated into the assessment of the tumor immune state of basal-like breast patients. |
| Databáze: | OpenAIRE |
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