1541P - Presence of tumor-specific cytolytic T cells in human primary breast carcinoma: consequences for immunotherapy

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Immunotherapy
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Therapy
Presenter David Schröder
Citation Annals of Oncology (2016) 27 (6): 526-544. 10.1093/annonc/mdw392
Authors D. Schröder1, J. Carrasco2, O. Bricard1, G. Hames1, N. Remy1, K. Missault1, J. Canon2, P. Vannuffel3, C. Galant4, M. Berlière4, P.G. Coulie1
  • 1Cellular Genetics Unit, de Duve Institute, 1200 - Bruxelles/BE
  • 2Department Of Medical Oncology / Translational Research Unit, Grand Hopital de Charleroi Site Notre Dame, Charleroi/BE
  • 3Centre De Génétique Humaine, Institut de Pathologie et de Génétique, Gosselies/BE
  • 4Breast Clinic, King Albert Ii Institute, Cliniques Universitaires St. Luc, Brussels/BE

Abstract

Background

Immunotherapy through stimulatory antibodies targeting the CTLA-4 or PD-1 pathways has a demonstrated clinical efficacy in a fraction of patients with various cancers. It is likely that the main immune effectors of these therapies are CD8+ cytolytic T lymphocytes (CTL) recognizing tumor-specific antigens. Highly antigenic tumors such as metastatic melanomas are often immunogenic, i.e. they stimulate spontaneous anti-tumor CTL responses. This immunogenicity, of which the presence of tumor-infiltrating T cells (TILs) is probably a surrogate marker, might be a predictive marker for clinical benefit to immunostimulatory antibodies. The immunogenicity of primary breast carcinomas for CD8+ T cells has not been studied, but the amounts of TILs have been positively correlated with patients' survival. Here we wished to obtain evidence for the presence of tumor-specific CD8+ T cells in TILs from primary breast carcinomas.

Methods

From 5 tumors (2 ER+/HER2, 2 ER+/HER2+, 1 ER/HER2) we isolated TILs and derived a random set of ±100 CD8+ T cell clones that we screened for recognition of candidate tumor-specific antigenic peptides selected through tumor exome sequencing and gene expression profiling. These peptides were encoded either by mutated genes or by cancer-germline genes.

Results

For 4 tumors, we screened 61-142 T cell clonotypes for recognition of 23-61 candidate mutated peptides, without any positive result. For the last tumor (ER+/HER2), 6 out of 57 T cell clonotypes recognized 4 out of 109 candidate mutated peptides but not the corresponding wild-type peptides. This tumor contained more mutations than the other four, and displayed microsatellite instability.

Conclusions

Some human primary breast carcinomas are immunogenic, as one tumor contained at least 10% of tumor-specific cells among the CD8+ TILs. Our observation corroborates the association between high mutation burden and CTL response to mutated tumor antigens. The presence of tumor-specific CD8+ suggests that the corresponding patient could benefit from the currently used immunostimulatory antibodies.

Clinical trial identification

code 0nco2008-01 - non interventional trial

Legal entity responsible for the study

Cliniques Universitaires Saint Luc

Funding

Cliniques Universitaires Saint Luc, Belgian Cancer Foundation, Fonds de la Recherche Scientifique

Disclosure

All authors have declared no conflicts of interest.