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Evaluation of radiofrequency ablation therapy combined with immune system checkpoint inhibitors in a murine model of renal cell carcinoma

Grant number: 18/14328-1
Support type:Regular Research Grants
Duration: April 01, 2021 - March 31, 2023
Field of knowledge:Health Sciences - Medicine - Surgery
Principal researcher:Walter Henriques da Costa
Grantee:Walter Henriques da Costa
Home Institution: A C Camargo Cancer Center. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil
Assoc. researchers:Amanda Braga de Figueiredo ; Kenneth John Gollob ; Tiago Góss dos Santos

Abstract

When diagnosed in advanced stages, renal cell carcinoma patients have a poor prognosis, with 20% 5-year survival rates. Immunotherapy based on checkpoint inhibitors has presented encouraging results in the treatment of several tumor types, and recently promising outcomes were observed in clinical trials of metastatic renal cell carcinoma. While immunotherapy has been successful in many patients, improvements are needed to attain better responses. Many approaches have been studied to sensitize less immunogenic tumors and the surgical method of radiofrequency ablation has been an important tool used in renal cancer. The aim of this study is to evaluate in a murine animal model the impact of thermal ablation of renal adenocarcinoma tumors and its potential to influence the host immune response when combined with systemic immunotherapeutic treatment. Balb/c animals will be inoculated with the Renca renal tumor cell line on both flanks and animals will submitted doradioablation in combination with systemic therapy with murine anti-PD1 and anti-CTLA-4 neutralizing antibodies. The rationale behind the study is that greater antigen presentation of tumor antigens induced by radiofrequencytissue injury will enhance the immune response. Combination therapy is expected to show superior outcomes in terms of outcomes and we will assess the immune response of the animals through Opal multiplex immunohistochemistry which permits labeling of up to 8 different markers and high-dimensional flow cytometry(FACSymphony) which permits the evaluation of 30 markers simultaneously. Together, these data will provide a robust analysis of the landscape of molecules involved in the host's immune response to the tumor. (AU)

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