Characterization of the cryoablation-induced immune response in kidney cancer patients.

Cryoablation is one of treatment modalities for kidney cancer and is expected to induce strong local immune responses as well as systemic T-cell-mediated immune reactions that may lead to the regression of distant metastatic lesions. Thus, the characterization of T cell repertoire and immune environment in tumors before and after treatment should contribute to the better understanding of the cryoablation-induced anticancer immune responses. In this study, we collected tumor tissues from 22 kidney cancer patients, before cryoablation and at 3 mo after cryoablation. In addition, blood samples were collected from 14 patients at the same time points. We applied a next generation sequencing approach to characterize T cell receptor β (TCRB) repertoires using RNAs isolated from tumor tissues and peripheral blood mononuclear cells. TCRB repertoire analysis revealed the expansion of certain T cell clones in tumor tissues by cryoablation. We also found that proportions of abundant TCRB clonotypes (defined as clonotypes with ≥ 1% frequency among total TCRB reads) were significantly increased in the post-cryoablation tissue samples than those of pre-cryoablation tumor samples. Some of these TCRB clonotypes were found to be increased in peripheral blood. Expression analysis of immune-related genes in the tissues of pre- and post-cryoablation showed significantly elevated transcriptional levels of CD8+ , CD4+ , Granzyme A (GZMA), and CD11c along with a high CD8/FOXP3 ratio in the post-cryoablation tissue samples. Our findings revealed that cryoablation could induce strong immune reactions in tumors with oligoclonal expansion of antitumor T cells, which circulate systemically.