Abstract
Abstract Cryoablation is one of promising treatment modalities for kidney cancer and expected to induce strong local immune response as well as systemic T cell-mediated immune reaction that may lead to regression of distant metastatic lesions. In this study, we collected tumor tissues from 14 kidney cancer patients, at the time points of pre-cryoablation and 3 months after cryoablation. In addition, blood samples were collected from 8 kidney cancer patients at the same time points. We applied a next generation sequencing approach to characterize T cell receptor beta (TCRB) repertoires using mRNA isolated from tumor tissues and peripheral blood mononuclear cells. To assess clonality of T cells, the diversity index of TCRB was calculated according to complementarity-determining region 3 sequences. Through TCRB repertoire analysis, we demonstrated expansion of certain T cell clones in tumor tissues by cryoablation. In addition, we found that proportions of abundant TCRB clonotypes (≥ 1% frequency among total TCRB reads) were significantly increased in the post-cryoablation tissue samples than those of pre-cryoablation tumor samples, suggesting that cryoablation could induce strong immune reactions in tumors with oligoclonal expansion of anti-tumor T cells. Interestingly, some of these TCRB clonotypes were also increased in peripheral blood, indicating that certain numbers of T cell clones may also circulate systemically and then attack tumor cells in distant regions. We also measured mRNA expression levels of immune-related genes in the tissue samples of pre- and post- cryoablation and found significantly elevated expression levels of CD8, CD4, Granzyme A, and CD11c along with high CD8/FOXP3 ratio in the post-cryoablation tissue samples. Furthermore, immunohistochemical analysis confirmed infiltration of a large number of CD11c-positive cells, probably representing macrophages and dendritic cells into the post-cryoablation tissues. Collectively, our findings revealed that cryoablation could induce both local and systemic immune responses associated with CD11c-positive cells infiltration and oligoclonal expansion of anti-tumor T cells. For the translation into clinics, unique TCR sequences identified in post-cryoablation tissues in individual patients can be applied to personalized TCR-engineered T cell therapy. Citation Format: Taigo Kato, Tomoyuki Iwasaki, Motohide Uemura, Akira Nagahara, Hiroki Higashihara, Keigo Osuga, Yuji Ikeda, Kazuma Kiyotani, Jae-Hyun Park, Norio Nonomura, Yusuke Nakamura. Characterization of the cryoablation-induced immune response in kidney cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4687. doi:10.1158/1538-7445.AM2017-4687
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