title: Carbon-ion beam treatment induces systemic antitumor immunity against murine squamous cell carcinoma.
abstract: BACKGROUND
  Carbon-ion beam (CIB) treatment is a powerful tool for controlling primary tumors in the clinical setting. However, to date, few clinical or experimental studies have investigated the effects of CIB treatment on tumor recurrence and antitumor immunity.
  
  
  METHODS
  A multiple challenge test was performed using syngenic and nude mouse models of a poorly immunogenic squamous cell carcinoma cell line (SCCVII) after CIB treatment at a clinically available dose (77 kiloelectron volts [keV]/microm) to primary tumors. To further examine changes in antitumor immunity in this model, the authors used dendritic cell (DC)-based immunotherapy.
  
  
  RESULTS
  In a syngenic model, CIB treatment itself resulted not only in efficient elimination of the primary tumor but also in a dramatic reduction of tumor formation after secondary tumor challenge at a contralateral site (P<.0001). Conversely, CIB treatment eliminated neither the primary nor the secondary tumor in nude mice. This antitumor effect produced by CIB treatment was enhanced significantly by combining it with DC immunotherapy (P=.0007). Combined CIB and DC treatment induced more intense cytolytic activity than CIB in a chromium-release assay. The third challenge tests, which included challenge with a third-party tumor cell line (FM3A) and effector depletion, revealed that the antitumor effects were the results of tumor-specific, long-lasting antitumor immunity through CD8-positive T lymphocytes.
  
  
  CONCLUSIONS
  To the authors' knowledge, this is the first demonstration of strong antitumor immunity induced by CIB treatment in a dermal tumor, and this effect was enhanced by combining it with DC-based immunotherapy. The authors concluded that this combination warrants further investigation as a promising modality for the prevention of tumor recurrence.
authors.affiliation: Department of Gene Therapy, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Akinao
authors.initials: A
authors.lastname: Matsunaga
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Ueda
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yamada
authors.forename: Yui
authors.initials: Y
authors.lastname: Harada
authors.forename: Hideaki
authors.initials: H
authors.lastname: Shimada
authors.forename: Mamoru
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Tsujii
authors.forename: Takenori
authors.initials: T
authors.lastname: Ochiai
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Yonemitsu
mesh_terms: D000818:Animals; D002244:Carbon; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D003713:Dendritic Cells; D005260:Female; D006084:Graft Rejection; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007477:Ions; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D007477:Ions; D002244:Carbon