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

ABSTRACT: 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.

SUBMITTER: Kato T

PROVIDER: S-EPMC5543848 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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

Kato Taigo T Iwasaki Tomoyuki T Uemura Motohide M Nagahara Akira A Higashihara Hiroki H Osuga Keigo K Ikeda Yuji Y Kiyotani Kazuma K Park Jae-Hyun JH Nonomura Norio N Nakamura Yusuke Y

Oncoimmunology 20170516 7

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 kidne ...[more]

PMID: 28811963

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Project description:Cancer treatment with doxorubicin (DOX) can induce cumulative dose-dependent cardiotoxicity. Currently, there are no specific biomarkers that can identify patients at risk during the initial doses of chemotherapy. The aim of this study was to examine plasma cytokines/chemokines and potential cardiovascular biomarkers for the prediction of DOX-induced cardiotoxicity. Plasma samples were collected before (T0), and after the first (T1) and the second (T2) cycles of DOX-based chemotherapy of 27 breast cancer patients, including five patients who presented with >10% decline of left ventricular ejection fraction (LVEF), five patients with LVEF decline of 5-10%, and 17 patients who maintained normal LVEF at the end of chemotherapy (240 mg/m2 cumulative dose of DOX from four cycles of treatment). Multiplex immunoassays were used to screen plasma samples for 40 distinct chemokines, nine matrix metalloproteinases, 33 potential markers of cardiovascular diseases, and the fourth-generation cardiac troponin T assay. The results showed that the patients with abnormal decline of LVEF (>10%) had lower levels of CXCL6 and sICAM-1 and higher levels of CCL23 and CCL27 at T0; higher levels of CCL23 and lower levels of CXCL5, CCL26, CXCL6, GM-CSF, CXCL1, IFN-γ, IL-2, IL-8, CXCL11, CXCL9, CCL17, and CCL25 at T1; and higher levels of MIF and CCL23 at T2 than the patients who maintained normal LVEF. Patients with LVEF decline of 5-10% had lower plasma levels of CXCL1, CCL3, GDF-15, and haptoglobin at T0; lower levels of IL-16, FABP3, and myoglobin at T1; and lower levels of myoglobin and CCL23 at T2 as compared to the patients who maintained normal LVEF. This pilot study identified potential biomarkers that may help predict which patients are vulnerable to DOX-induced cardiotoxicity although further validation is needed in a larger cohort of patients. Impact statement Drug-induced cardiotoxicity is one of the major concerns in drug development and clinical practice. It is critical to detect potential cardiotoxicity early before onset of symptomatic cardiac dysfunction or heart failure. Currently there are no qualified clinical biomarkers for the prediction of cardiotoxicity caused by cancer treatment such as doxorubicin (DOX). By using multiplex immunoassays, we identified proteins with significantly changed plasma levels in a group of breast cancer patients who were treated with DOX-based chemotherapy and produced cardiotoxicity. These proteins were associated with immune response and were identified before DOX treatment or at early doses of treatment, thus they could be potential predictive biomarkers of cardiotoxicity although further validation is required to warrant their clinical values.

Dataset Information

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

Publications

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

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