Identification of patient-specific and tumor-shared T cell receptor sequences in renal cell carcinoma patients

// Chiara Massa 1 , Harlan Robins 2 , Cindy Desmarais 2 , Dagmar Riemann 1 , Corinna Fahldieck 1 , Paolo Fornara 3 , Barbara Seliger 1 1 Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, Halle, Saale 06112, Germany 2 Adaptive Biotechnologies Corp, Seattle, WA 98102, USA 3 Clinic of Urology, Martin Luther University Halle-Wittenberg, Halle, Saale 06112, Germany Correspondence to: Barbara Seliger, email: barbara.seliger@uk-halle.de Keywords: TCR sequencing, renal cell carcinoma, immune response, immune monitoring, immune therapy Received: October 25, 2016      Accepted: January 09, 2017      Published: February 03, 2017 ABSTRACT A major requirement for cancer immunotherapy is the development of biomarkers for prognosis and for monitoring therapy response. In an attempt to evaluate the immune response of renal cell carcinoma (RCC) patients, tumor lesions and / or blood samples from 12 RCC patients underwent deep T cell receptor (TCR) sequencing. Despite the low number of samples, different TCR distribution patterns could be detected. Most of the RCC patients presented “patient-specific” TCR sequences, and those clonotypes were present at higher frequency in tumor lesions suggesting a specific extravasation from the blood. Comparison among the tumor samples revealed also “patient-shared” TCR patterns. Indeed, a central core of 16 different TCRs were shared by 3 patients, whereas other 6 patients shared between 4 and 6 TCR sequences, with two sub-groups sharing 12 to 17 different clonotypes. The relative frequencies of shared clonotypes were very different varying from < 1% to a maximum of 37% of the total TCR repertoire. These data confirm the presence of tumor-specific TCR within the cancer tissue and suggest the existence of shared epitopes among different patients that might be used as targets for tumor immunotherapy.