Login to Access Video or Poster Abstract: MP16-18
Sources of Funding: This work was supported by Jiangsu Graduate Student Innovation Grant (No.KYZZ15_0066) and Excellent Doctoral Dissertations Cultivation Fund from Southeast University.

Introduction

Novel antibodies against immune checkpoint proteins, which led to unleash anti-tumor T cell responses, results in durable long-lasting responses but only in a fraction of patients. RFA of tumors can enhance systemic antitumor immunity through a series of mechanisms. Nevertheless, antitumor immunity induced by RFA is mostly weak and not sufficient enough to eradicate metastatic tumors completely or prevent disease progression durably. We hypothesized that these two different treatment strategies could act synergistically. The purpose of this study is to evaluate whether the combination of RFA and anti-PD-1 antibody could result in both primary tumor control and prevention of lung metastasis in a murine model bearing renal adenocarcinoma.

Methods

Balb/c mice were injected with Renca cells into their left kidney to establish the orthotopical model of renal cancer. One week later, the mice were injected intravenously with Renca cells, which afterwards would spread into various organs particularly into the lung. Then, the mice were treated with IgG alone, anti-PD-1 monoclonal antibodies (mAbs), surgical resection/RFA of the kidney tumor, or surgical resection / RFA + anti-PD-1. anti-PD-1 mAbs were administered by intravenous injection (i.v) every other day for three times. The antitumor effect of the treatment was evaluated by counting the numbers of the tumors in the lung, weighing the lungs and observing the survival time, and the immunological responses were assessed using peripheral blood immune parameters and analyzing the infiltration of CD+4 or CD+8 T cells into the tumors.

Results

Treatment of mice bearing kidney tumors with RFA and anti-PD-1 mAbs resulted in significantly greater growth suppression of primary kidney tumors and prolonged survival compared with mice treated with the other modalities. ELISA analysis showed that mice treated with RFA and i.v anti-PD-1 mAbs had higher level of IFN-γ, TNF-α in the peripheral blood after treatment compared with the other groups. In the combination therapy group, growth of lung metastases was prevented with fewer numbers of lung metastases and lighter weight of lung. The combined therapy of RFA and anti-PD-1 antibodies significantly increased T-cell infiltration, especially the effector T cells, which upregulated the effector T cells to regulatory T cells ratio.

Conclusions

The combination of RFA and anti-PD-1 mAbs resulted in stronger antitumor immunity and prolonged survival in this pre­clinical model of advanced RCC.

Funding

This work was supported by Jiangsu Graduate Student Innovation Grant (No.KYZZ15_0066) and Excellent Doctoral Dissertations Cultivation Fund from Southeast University.