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
2600 - Atezolizumab (atezo) vs chemotherapy (chemo) in patients (pts) with platinum-treated locally advanced or metastatic urothelial carcinoma (mUC): a long-term overall survival (OS) and safety update from the Phase III IMvigor211 study
Presenter: Michiel Van der Heijden
Session: Poster Display session 3
Resources:
Abstract
3598 - Three-Year Follow-Up From the Phase 3 KEYNOTE-045 Trial: Pembrolizumab (Pembro) Versus Investigator’s Choice (Paclitaxel, Docetaxel, or Vinflunine) in Recurrent, Advanced Urothelial Cancer (UC)
Presenter: Andrea Necchi
Session: Poster Display session 3
Resources:
Abstract
2382 - First Report of Efficacy and Safety From a Phase 2 Trial of Tislelizumab, an Anti-PD-1 Antibody, for the Treatment of PD-L1+ Locally Advanced or Metastatic Urothelial Carcinoma (UC) in Asian Patients
Presenter: Dingwei Ye
Session: Poster Display session 3
Resources:
Abstract
2388 - Quality of Life of Metastatic Urothelial Cancer (mUC) Patients Treated with Enfortumab Vedotin (EV) Following Platinum-Containing Chemotherapy and a Checkpoint Inhibitor (CPI): Data from EV-201 Cohort 1
Presenter: Bradley McGregor
Session: Poster Display session 3
Resources:
Abstract
3748 - Safety and efficacy of atezolizumab (atezo) in patients (pts) with autoimmune disease (AID): subgroup analysis of the SAUL study in locally advanced/metastatic urinary tract carcinoma
Presenter: Yohann Loriot
Session: Poster Display session 3
Resources:
Abstract
1126 - Validation of the VIO prognostic index in patients with metastatic urothelial carcinoma treated with immune-checkpoint inhibitors
Presenter: Rafael Morales Barrera
Session: Poster Display session 3
Resources:
Abstract
3693 - Pathologic outcomes after neoadjuvant chemotherapy for high-risk muscle invasive bladder cancer
Presenter: Justin Matulay
Session: Poster Display session 3
Resources:
Abstract
4840 - Analysis of response to prior therapies and therapies after treatment with erdafitinib in fibroblast growth factor receptor (FGFR)-positive patients (pts) with metastatic urothelial carcinoma (mUC)
Presenter: Arlene Siefker-Radtke
Session: Poster Display session 3
Resources:
Abstract
1221 - Clinical outcomes by sex with atezolizumab (atezo) monotherapy in patients (pts) with locally advanced/metastatic urothelial carcinoma (mUC)
Presenter: Jean Hoffman-censits
Session: Poster Display session 3
Resources:
Abstract
1715 - National Small Cell Bladder Cancer Audit: Results from 26 UK institutions
Presenter: Caroline Chau
Session: Poster Display session 3
Resources:
Abstract