Intratumoral T cell receptor beta repertoire as a biomarker in head and neck squamous cell carcinoma

In this study, we examine the T cell receptor (TCR) repertoire in a cohort of Head and Neck Squamous Cell Carcinoma (HNSCC) patients (n=50) at time of diagnosis. The TCR repertoire is indicative of the ability of the body to mount an immune response, with increased productive clonality within the tumor environment suggesting accumulation of tumor antigen specific T cells. Recent studies demonstrate that the intratumoral TCR repertoire is prognostic of response to anti-PD-1 (Tumeh et al., 2014) and anti-CTLA-4 (Page et al., 2016) therapies. Here we examine diversity and clonality of intratumoral T cell β repertoires in HNSCC patients independently and in conjunction with other biomarkers including tumor mutational burden/neoantigen load, expression of inhibitory checkpoints, and characterization of immune cell populations, as well as clinical metadata including HPV status, smoking history, and survival outcomes. The TCRβ repertoire was analyzed from FFPE primary tumor samples through targeted next generation DNA sequencing of the TCRβ loci and examination of the CDR3 sequences to determine clonality of the TCRβ repertoire (1 – Pielou’s evenness). Somatic genomic alterations, tumor mutational burden, and HLA typing were conducted through whole exome sequencing. Inhibitory checkpoint expression and characterization of immune cell populations were conducted through immunohistochemistry, RNA expression, or both methods. Preliminary results indicate productive clonality of the TCR repertoire in the range of 0.03-0.16. In examining HPV+ and HPV- patients, where we hypothesize the presentation of foreign peptides of viral etiology will produce an increase in T cell populations recognizing those neoantigens, we see no difference in either T cell infiltration or productive clonality. However, we observe that PD-L1 status is significantly correlated ( p Citation Format: Lara McGrath, Elizabeth Maloney, Maria Secrier, Helen Angell, Emma Jones, Brian Dougherty, Daniel Stetson, Patricia McCoon, Andrew Pierce, Craig Barker, Carl Barrett. Intratumoral T cell receptor β repertoire as a biomarker in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr B83.