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Poster Display session 3

1743 - Expression of MHC class I, HLA-A and HLA-B identifies immune activated breast tumors with favorable outcome

Date

30 Sep 2019

Session

Poster Display session 3

Topics

Immunotherapy

Tumour Site

Breast Cancer

Presenters

María Del Mar Noblejas López

Citation

Annals of Oncology (2019) 30 (suppl_5): v475-v532. 10.1093/annonc/mdz253

Authors

M.D.M. Noblejas López1, C. Nieto-Jiménez1, S. Morcillo-García1, J. Pérez-Peña1, M. Nuncia-Cantarero1, E.M. Galán-Moya2, E. Amir3, A. Pandiella4, B. Győrffy5, A. Ocaña6

Author affiliations

  • 1 Oncología Traslacional, Complejo Hospitalario Universitario de Albacete, 02006 - Albacete/ES
  • 2 Oncología Traslacional, Universidad de Castilla-La Mancha, 02006 - Albacete/ES
  • 3 Medical Oncology And Hematology, Princess Margaret Cancer Center, M5G 2M9 - Toronto/CA
  • 4 Centro De Investigación Del Cáncer, CSIC, 37007 - Salamanca/ES
  • 5 Institute Of Enzymology, MTA TTK Lendület Cancer Biomarker Research Group, Budapest/HU
  • 6 Servicio Oncología Médica Unidad De Nuevas Terapias Y Oncología Traslacional, Hospital Clínico San Carlos, 28040 - Madrid/ES

Resources

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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.

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