Analysis of T-cell repertoires in early-stage breast carcinomas to evaluate tumor immunogenicity.

Authors

null

Javier Carrasco

Grand Hôpital de Charleroi, Charleroi, Belgium

Javier Carrasco , David Schröder , Christine Galant , Martine Berliere , Jean-Luc Re Canon , Jean-Pascal H. Machiels , Paul Delrée , Pascale Hilbert , Francois P. Duhoux , Isabelle Bar , Pierre Coulie

Organizations

Grand Hôpital de Charleroi, Charleroi, Belgium, De Duve Institute, Université Catholique de Louvain, Brussels, Belgium, Cliniques Universitaires Saint Luc, Brussels, Belgium, Department of Gynecology, King Albert II Cancer Institute, Cliniques Universitaires Saint-Luc, Brussels, Belgium, Institut Roi Albert II, Service d’Oncologie Médicale, Cliniques Universitaires Saint-Luc and Institut de Recherche Clinique et Expérimentale (Pole MIRO), Université Catholique de Louvain, Brussels, Belgium, Institut de Pathologie et de Génétique, Gosselies, Belgium, Department of Medical Oncology, King Albert II Cancer Institute, Cliniques universitaires Saint-Luc and Institut de Recherche Expérimentale et Clinique (Pôle MIRO), Université Catholique de Louvain, Brussels, Belgium, Translational Research Unit GHdC, IPG, Gosselies, Belgium, Duve Institute UCL Brussels, Brussels, Belgium

Research Funding

Other

Background: Breast carcinomas (BC) are often considered to be weakly immunogenic and thus poorly sensitive to immunotherapy. Methods: We analyzed the repertoire of tumor-infiltrating T cells (TILs) in 41 early BC by sequencing their T cell receptor β genes (TCRβ). Libraries were built using a digital sequencing approach, barcoding each sequenced molecule to improve accuracy and quantification. T cell repertoires were also obtained from paired blood samples allowing identification of T cell clones enriched in the tumors as compared to blood. For 5 patients, CD8+ TILs were cloned ex-vivo from a tumor sample and screened for recognition of autologous predicted neoepitopes. Results: T cell infiltration differed from one tumor to another. Its amount varied of more than 30 fold and its diversity ranged from < 100 to > 5000 different clonotypes. In 34% of the tumors, there was an important T cell infiltration and we detected several clonotypes with a ≥500 fold enrichment as compared to blood. In 22% of the tumors, an important T cell infiltration was observed but without significantly enriched clonotypes. In 43% of the tumors the T cell infiltration was very limited. For 5 tumors with a high T cell infiltration, we screened ex-vivo isolated CD8+ T cell clones for recognition of predicted neoepitopes. In 4 of these tumors, with no enriched clonotypes, no recognition was observed. In 1 of these tumors, with enriched clonotypes, 6 different CD8+ T cell clones recognized 4 predicted neoepitopes. Three of these clones were > 100 fold more frequent in the tumor as compared to blood. Conclusions: About 30% of early BC were infiltrated by T cell clonotypes significantly enriched relative to blood. In one of these tumors some of the most enriched clonotypes recognized neoepitopes, demonstrating that some primary BC are spontaneously immunogenic. About 20% of the tumors had an important T cell infiltration without enriched clonotypes. None of the TIL clones isolated from 4 such tumors recognized predicted neoepitopes. Our results suggest that the detection of intratumorally enriched T cell clonotypes could identify immunogenic tumors, which may be sensitive to treatment with immunostimulatory antibodies.

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Abstract Details

Meeting

2017 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Tumor Biology

Track

Tumor Biology

Sub Track

Immunobiology

Citation

J Clin Oncol 35, 2017 (suppl; abstr 11554)

DOI

10.1200/JCO.2017.35.15_suppl.11554

Abstract #

11554

Poster Bd #

254

Abstract Disclosures

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