title: Cryo-ablation improves anti-tumor immunity through recovering tumor educated dendritic cells in tumor-draining lymph nodes.
abstract: BACKGROUND
  In addition to minimally invasive destruction of tumors, cryo-ablation of tumors to some extent modulated anti-tumor immunity. Cryo-ablated tumors in glioma mice models induced anti-tumor cellular immunologic response which increases the percentage of CD3(+) and CD4(+)T cells in blood as well as natural killer cells. As a crucial role in triggering anti-tumor immunity, dendritic cells (DCs) were educated by tumors to adopt a tolerance phenotype which helps the tumor escape from immune monitoring. This study aims to study whether cryo-ablation could influence the tolerogenic DCs, and influence anti-tumor immunity in tumor-draining lymph nodes (TDLNs).
  
  
  METHODS
  Using the GL261 subcutaneous glioma mouse model, we created a tumor bearing group, cryo-ablation group, and surgery group. We analyzed alteration in phenotype and function of tolerogenic DCs, and evaluated the factors of anti-tumor immunity inhibition.
  
  
  RESULTS
  DCs in TDLNs in GL261 subcutaneous glioma mouse model expressed tolerogenic phenotype. In contrast to surgery, cryo-ablation improved the quantity and quality of these tolerogenic DCs. Moreover, the DCs decreased the expression of intracellular interleukin-10 (IL-10) and extra-cellular IL-10. In vitro, DCs from the cryo-ablation group recovered their specific function and induced potent anti-tumor immunity through triggering T cells. In vivo, cryo-ablation showed weak anti-tumor immunity, only inhibiting the growth of rechallenged tumors. But many IL-10-low DCs, rather than IL-10-high DCs, infiltrated the tumors. More importantly, Tregs inhibited the performance of these DCs; and depletion of Tregs greatly improved anti-tumor immunity in vivo.
  
  
  CONCLUSIONS
  Cryo-ablation could recover function of tumor induced tolerogenic DCs in vitro; and depletion of Tregs could improve this anti-tumor effect in vivo. The Tregs/CD4(+)T and Tregs/CD25(+)T cells in TDLNs inhibit DCs' activity and function.
authors: Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China ; The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Southern Medical University, Guangzhou, People's Republic of China.
authors: Xiao-Zheng
authors: XZ
authors: He
authors: Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China ; The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Southern Medical University, Guangzhou, People's Republic of China.
authors: Qi-Fu
authors: QF
authors: Wang
authors: Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors: Shuai
authors: S
authors: Han
authors: Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China ; The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Southern Medical University, Guangzhou, People's Republic of China.
authors: Hui-Qing
authors: HQ
authors: Wang
authors: Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China ; The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Southern Medical University, Guangzhou, People's Republic of China.
authors: Yong-Yi
authors: YY
authors: Ye
authors: Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China ; The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Southern Medical University, Guangzhou, People's Republic of China.
authors: Zhi-Yuan
authors: ZY
authors: Zhu
authors: Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China ; The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Southern Medical University, Guangzhou, People's Republic of China.
authors: Shi-Zhong
authors: SZ
authors: Zhang
mesh_terms: D000818:Animals; D003452:Cryosurgery; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D004195:Disease Models, Animal; D005910:Glioma / Q000276:immunology* / Q000473:pathology / Q000601:surgery*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL
keywords: anti-tumor immunity; cryo-ablation; dendritic cells; glioma; tumor-draining lymph nodes