title: Immunologic response to cryoablation of breast cancer.
abstract: OBJECTIVE
  With improvements in breast imaging and image-guided interventions, there is interest in ablative techniques for breast cancer. Cryosurgery initiates inflammation and leaves tumor-specific antigens intact, which may induce an anti-tumor immune response. To help define the mechanisms involved in the cryoimmunologic response, we compared cryosurgery to surgery in a murine model of breast cancer.
  
  
  METHODS
  BALB/c mice with MT-901 tumors underwent cryoablation or resection. Mice successfully treated were re-challenged with MT-901 or RENCA. Serum cytokine levels were analyzed by ELISA. Tumor draining lymph nodes (TDLN) and spleens were harvested, lymphocytes were activated and assessed for a specific anti-tumor response by both an interferon-gamma (IFNgamma) release assay and ELISPOT. NK cell activity was assessed by cytotoxicity against YAC-1, an NK-susceptible cell line.
  
  
  RESULTS
  After re-challenge, tumors developed in 86% of mice treated by surgical excision compared to 16% of mice treated by cryosurgery (p=0.025). Cryoablation of MT-901 had no effect on re-challenge with RENCA. Cryoablation led to significantly higher levels of interleukin (IL)-12 (383.6 pg/ml +/- 32.8 versus 251.6 +/- 16.5, p=0.025) and IFN-gamma (1564 pg/ml +/- 49 versus 1244 pg/ml +/- 101, p=0.009), but no changes in IL-4 or IL-10. Tumor-specific T-cell responses were evident after cryosurgery in lymphocytes from TDLN but not from spleen. Cryoablation also increased NK activity compared to surgery (24.5% +/- 17.3 versus 16.5% +/- 5.9, p < 0.001).
  
  
  CONCLUSIONS
  Cryoablation results in the induction of both a tumor-specific T-cell response in the TDLN and increased systemic NK cell activity, which correlates with rejection of tumors upon re-challenge.
authors.affiliation: University of Michigan, 3304 Cancer Center, East Medical Center, 1500 East Medical Center, Ann Arbor, MI 48109-0932, USA. msabel@umich.edu
authors.forename: Michael S
authors.initials: MS
authors.lastname: Sabel
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Nehs
authors.forename: Gang
authors.initials: G
authors.lastname: Su
authors.forename: Kathleen P
authors.initials: KP
authors.lastname: Lowler
authors.forename: James L M
authors.initials: JL
authors.lastname: Ferrara
authors.forename: Alfred E
authors.initials: AE
authors.lastname: Chang
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000276:immunology* / Q000601:surgery*; D003452:Cryosurgery; D016207:Cytokines / Q000097:blood; D003602:Cytotoxicity, Immunologic; D005260:Female; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000097:blood; D007694:Killer Cells, Natural / Q000378:metabolism; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D016207:Cytokines; D007371:Interferon-gamma