title: Microwave ablation combined with OK-432 induces Th1-type response and specific antitumor immunity in a murine model of breast cancer.
abstract: Minimally invasive therapies, such as microwave ablation (MWA), are widely used for the treatment of solid tumors. Previous studies suggest that MWA is feasible for the treatment of small breast cancer, and thermal ablation may induce adaptive antitumor immunity. However, the induced immune responses are mostly weak, and the immunomodulation effects of MWA in breast cancer are unclear. Immunostimulant OK-432 can induce tumor-specific T-cell responses and may augment the immunity induced by MWA.
  
  
  
  We treated 4T1 breast cancer bearing BALB/c mice with MWA, OK-432, MWA plus OK-432, or left without treatment. Survival time was evaluated with the Kaplan-Meyer method comparing survival curves by log-rank test. On day 25 after ablation, surviving mice received tumor rechallenge, and the rechallenged tumor volumes were calculated every 5 days. Immunohistochemistry and flow cytometry were used to evaluate the T-cell immune responses in ablated tissues and spleens. The tumor-specific immunity was assessed by enzyme-linked immunospot assays. Besides, the cytokine patterns were identified from enzyme-linked immunosorbent assay.
  
  
  
  Microwave ablation plus OK-432 resulted in longer survival than single treatment and protect most surviving mice from tumor rechallenge. Both local and systemic T-cell responses were induced by MWA and were further enhanced by subsequent administration of OK-432. Moreover, the combination of MWA and OK-432 induced stronger tumor-specific immune responses than MWA alone. In addition, OK-432 and MWA synergistically promoted the production of Th1-type but not Th2-type cytokines, and polarized T-cell responses to Th1-dominant state.
  
  
  
  The T-cell immune responses were activated by MWA in breast cancer. Furthermore, the combination of MWA and OK-432 induced Th1-type response and elicited specific antitumor immunity.
authors.affiliation: Department of Breast Surgery, the First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Breast Surgery, the First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Breast Surgery, the First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Pan
authors.affiliation: Department of Breast Surgery, the First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Ma
authors.affiliation: Department of Breast Surgery, the First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Breast Surgery, the First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Breast Surgery, the First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
authors.forename: Xiaoan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Breast Surgery, the First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ding
authors.affiliation: Department of Breast Surgery, the First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China. zhouwenbin@njmu.edu.cn.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Breast Surgery, the First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China. ws0801@hotmail.com.
authors.forename: Shui
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D016764:Cell Polarity / Q000187:drug effects; D003131:Combined Modality Therapy; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D053208:Kaplan-Meier Estimate; D015674:Mammary Neoplasms, Animal / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D008807:Mice, Inbred BALB C; D008872:Microwaves; D010844:Picibanil / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*
chemical_list: D016207:Cytokines; D010844:Picibanil
keywords: Breast cancer; Immunotherapy; Microwave ablation; OK-432; T cell