T-bet And Eomes Are Required For Radiofrequency Ablation Induced Anti-tumor Immune Response

Objective To evaluate the role of transcription factor T-bet(T-box expressed in T cells) and Eomes(Eomesodermin) in Radiofrequency ablation(RFA) induced anti-tumor immune response.Methods C57BL/6 mice were inoculated with B16 melonoma cells on bilateral flanks, and RFA was performed for tumors on the right flank. Immunohistochemical staining analysis of the right tumor tissue 3 days after RFA. Obtain The number and subset of the lymphocytes infiltrating into the tumor on the left flank were analyzed by flow cytometry(FCM). The m RNA levels of several cytokines and transcription factors were tested by quantitative real-time PCR. The expressions of T-bet and Eomes in T cells and NK cells were also analyzed by FCM. In addition, we established RFA treatment model in T-bet-/-(TKO), Eomes-/-(EKO) and wild-type C57BL/6 mice. The growth curve of the left tumor and survival curve of mice were recorded, respectively.Results RFA suppresses the growth of tumor outside the ablation zone. The number of CD45+, CD4+, CD8+ T cell, NK and CD4+Fox P3- cells infiltrating into the tumor on the left flank was significantly increased in RFA-treated mice. The m RNA level of IL-2, IFN-γ, TNF-α, T-bet and Eomes was upregulated in the tumor on the left flank after RFA. At the same time, the ratio of T cell and NK cell expressing T-bet and Eomes was increased both in tumor and spleen after RFA. In addition, we found that RFA induced an inhibition of tumor growth on the contralateral flank and prolonged the survival of tumor-bearing mice. T-bet or Eomes knockout significantly weakened the anti-tumor immune responses induced by RFA.Conclusions T-bet and Eomes play an important role in anti-tumor immune responses induced by RFA.