title: Immune Adjuvant Activity of Pre-Resectional Radiofrequency Ablation Protects against Local and Systemic Recurrence in Aggressive Murine Colorectal Cancer.
abstract: OBJECTIVE
  While surgical resection is a cornerstone of cancer treatment, local and distant recurrences continue to adversely affect outcome in a significant proportion of patients. Evidence that an alternative debulking strategy involving radiofrequency ablation (RFA) induces antitumor immunity prompted the current investigation of the efficacy of performing RFA prior to surgical resection (pre-resectional RFA) in a preclinical mouse model.
  
  
  METHODS
  Therapeutic efficacy and systemic immune responses were assessed following pre-resectional RFA treatment of murine CT26 colon adenocarcinoma.
  
  
  RESULTS
  Treatment with pre-resectional RFA significantly delayed tumor growth and improved overall survival compared to sham surgery, RFA, or resection alone. Mice in the pre-resectional RFA group that achieved a complete response demonstrated durable antitumor immunity upon tumor re-challenge. Failure to achieve a therapeutic benefit in immunodeficient mice confirmed that tumor control by pre-resectional RFA depends on an intact adaptive immune response rather than changes in physical parameters that make ablated tumors more amenable to a complete surgical excision. RFA causes a marked increase in intratumoral CD8+ T lymphocyte infiltration, thus substantially enhancing the ratio of CD8+ effector T cells: FoxP3+ regulatory T cells. Importantly, pre-resectional RFA significantly increases the number of antigen-specific CD8+ T cells within the tumor microenvironment and tumor-draining lymph node but had no impact on infiltration by myeloid-derived suppressor cells, M1 macrophages or M2 macrophages at tumor sites or in peripheral lymphoid organs (i.e., spleen). Finally, pre-resectional RFA of primary tumors delayed growth of distant tumors through a mechanism that depends on systemic CD8+ T cell-mediated antitumor immunity.
  
  
  CONCLUSIONS
  Improved survival and antitumor systemic immunity elicited by pre-resectional RFA support the translational potential of this neoadjuvant treatment for cancer patients with high-risk of local and systemic recurrence.
authors.affiliation: Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York, United States of America.|Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, New York, United States of America.|Department of Surgery, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Fumito
authors.initials: F
authors.lastname: Ito
authors.affiliation: Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
authors.forename: Amy W
authors.initials: AW
authors.lastname: Ku
authors.affiliation: Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Bucsek
authors.affiliation: Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York, United States of America.|Department of Urology, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
authors.forename: Jason B
authors.initials: JB
authors.lastname: Muhitch
authors.affiliation: Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York, United States of America.|Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Trupti
authors.initials: T
authors.lastname: Vardam-Kaur
authors.affiliation: Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York, United States of America.|Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
authors.forename: Minhyung
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Fisher
authors.affiliation: Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
authors.forename: Marta
authors.initials: M
authors.lastname: Camoriano
authors.affiliation: Department of Pathology, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
authors.forename: Thaer
authors.initials: T
authors.lastname: Khoury
authors.affiliation: Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Skitzki
authors.affiliation: Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
authors.forename: Sandra O
authors.initials: SO
authors.lastname: Gollnick
authors.affiliation: Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
authors.forename: Sharon S
authors.initials: SS
authors.lastname: Evans
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000941:Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D017115:Catheter Ablation; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology / Q000601:surgery*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000517:prevention & control*; D016019:Survival Analysis; D059016:Tumor Microenvironment / Q000187:drug effects
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D016207:Cytokines