Abstract 1743
Background
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.
Methods
We used data from KM Plotter to develop an exploratory cohort and then utilized information from Cancer Genome Atlas (TCGA) and METABRIC to create two validation cohorts. Raw data were re-processed and analyzed using plyr R and Bioconductor. Definition of molecular subtypes as well as identification of mutations was performed using RNAseq from TCGA. We used NetMHC 4.0 epitope-HLA to predict binding to MHC I molecules. Cox proportional hazards regression was computed to correlate gene expression and survival outcome. Multiple genes were combined into a signature by using their mean expression.
Results
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 dataset (OS HLA-A, HR: 0.59, CI 0.42-0.82; p = 0.002; HLA-B, HR: 0.60, CI 0.44-0.82; p = 0.001); and in the TCGA dataset (OS HLA-A, HR: 0.34, CI 0.16-0.75; p = 0.005; HLA-B, HR: 0.21, CI 0.01-0.71; p = 0.005). 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 (IFN gamma signature, expanded immune gene signature and Cytotoxic T lymphocyte). Several neopeptides expressed in breast cancer were also identified including FUK, SNAPC3, GC, ANO8, DOT1L, HIST1H3F, MYBPH, STX2, FRMD6, CPSF1, or SMTN, among others.
Conclusions
Expression of HLA-A and B is associated with T cell activation and identifies immune activated, basal-like breast cancers with favorable prognosis.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Instituto de Salud Carlos III (PI16/01121), ACEPAIN; Diputación de Albacete, CIBERONC, CRIS Cancer Foundation, scientific foundation of the AECC, implementation research program of the UCLM Spanish System of Science, Technology and Innovation-Secti (co-funded by the European Commission/FSE funds).
Disclosure
A. Ocaña: Research grant / Funding (institution): Entrechem; Travel / Accommodation / Expenses: Merck. All other authors have declared no conflicts of interest.
Resources from the same session
5822 - Greek nursing students experience facing death in clinical practice
Presenter: Maria Dimoula
Session: Poster Display session 3
Resources:
Abstract
2866 - HOPEVOL: Hospice care appropriate to the wishes and needs of patients in the palliative terminal phase.
Presenter: Merel van Klinken
Session: Poster Display session 3
Resources:
Abstract
829 - Mindfulness-based stress reduction in early palliative care for advanced cancer patients : an italian single-centre study. MINDEEP
Presenter: Emilia Gianotti
Session: Poster Display session 3
Resources:
Abstract
2702 - Optimising Inpatient Oncology Care
Presenter: Lisa Judge
Session: Poster Display session 3
Resources:
Abstract
1527 - Analysis on the Implementation Results of Family Sickbed for Oncology Patients in Dongshi Township Health Centers from 2015 to 2017
Presenter: Yayu Huang
Session: Poster Display session 3
Resources:
Abstract
2054 - Exploring needs for palliative care and quality of life for oncology patients with advanced disease who undergo radiotherapy
Presenter: Foteini Antonopoulou
Session: Poster Display session 3
Resources:
Abstract
5605 - Cytotoxic contamination in cancer care settings – Risks and safety awareness among cancer nurses
Presenter: Sandra Lundman Vikberg
Session: Poster Display session 3
Resources:
Abstract
5769 - Understanding Chemotherapy - group education sessions prior to commencing chemotherapy
Presenter: Aileen McHale
Session: Poster Display session 3
Resources:
Abstract
2620 - Estimation of HPQ-based absenteeism and presenteeism in cancer patients via ResearchKit
Presenter: Shunsuke Kondo
Session: Poster Display session 3
Resources:
Abstract
4705 - Identifying falls-related variables and risk factors in hospitalised cancer patients
Presenter: Maria Montserrat Martí Dillet
Session: Poster Display session 3
Resources:
Abstract