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

Chiara Massa,Dagmar Riemann,Cindy Desmarais,Paolo Fornara,Harlan Robins,Barbara Seliger,Corinna Fahldieck

doi:10.18632/oncotarget.15064

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.

Highlights

Renal cell carcinoma (RCC) occurs with an incidence of 2-3% and is the 10th most common cancer type [1, 2]
Among them we found patient-specific sequences, that could target single tumor-restricted mutations important in the setting of personalized therapy, and various T cell receptor (TCR) that were shared by more patients and that might target widespread expressed RCC-associated tumor antigens
The TCR repertoire of tumor infiltrating and circulating lymphocytes was evaluated in 12 RCC patients that underwent surgical removal of the primary tumor in the Urology Department of the University Clinic of the Martin Luther University

Summary

Introduction

Renal cell carcinoma (RCC) occurs with an incidence of 2-3% and is the 10th most common cancer type [1, 2]. While the 5-year survival rate for localized RCC is above 70%, it drops to 12% when the disease has spread to distant organs, which is the case in more than half of the patients at presentation [2]. In the search for alternative or complementation therapies to surgical eradication for patients with advanced disease, the introduction of novel targeted agents has resulted in a better management of metastatic RCC [3, 4]. The therapeutic options targeting the VHL/HIF pathway with different tyrosine kinase inhibitors did improve the overall and progressionfree survival, durable complete responses remain elusive [5, 6]. In the setting of adjuvant immunotherapy, the long-term use of the cytokines interleukin (IL)-2 [7]

Methods

Results

Conclusion