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
3839 - Fenofibrate impairs pro-tumorigenic potential of cancer stem cell-like cells within drug-resistant prostate cancer cell populations.
Presenter: Tomasz Wróbel
Session: Poster Display session 3
Resources:
Abstract
3842 - Effect of docetaxel-resistance on the reactivity of prostate cancer cells to metformin
Presenter: Jessica Catapano
Session: Poster Display session 3
Resources:
Abstract
5198 - Cell plasticity and taxanes resistance in metastatic prostate cancer: ESRP1 as a predictive biomarker of taxane response
Presenter: Natalia Jimenez
Session: Poster Display session 3
Resources:
Abstract
2981 - Effect of Selumetinib plus AZD8186 treatment on Cabazitaxel sensitivity in docetaxel-acquired resistant metastatic prostate cancer cell lines
Presenter: Vicenc Ruiz de Porras
Session: Poster Display session 3
Resources:
Abstract
2779 - Anti-tumor activity of cediranib, a pan-inhibitor of vascular endothelial growth factor receptors, in pancreatic ductal adenocarcinoma cells
Presenter: Majid Momeny
Session: Poster Display session 3
Resources:
Abstract
1782 - The molecular mechanisms of EpCAM in regulating tumor progression and development of anti-EpCAM antibodies for colon cancer diagnosis and therapy
Presenter: Han-chung Wu
Session: Poster Display session 3
Resources:
Abstract
1322 - Detection of microRNAs as biomarker for anti-EGFR antibody resistance in colon cancer patients
Presenter: Jens Hahne
Session: Poster Display session 3
Resources:
Abstract
1579 - Serum exosomal microRNA-199b-5p as a novel circulating biomarker to predict response of preoperative chemoradiotherapy for locally advanced rectal cancer
Presenter: Dong Won Baek
Session: Poster Display session 3
Resources:
Abstract
1761 - Live biobank of patient-derived organoids from Thai colorectal cancer patients enables clinical outcome prediction
Presenter: Pariyada Tanjak
Session: Poster Display session 3
Resources:
Abstract
3542 - The biological implications of PDCD6 dysregulation in colorectal cancer
Presenter: Romina Briffa
Session: Poster Display session 3
Resources:
Abstract