title: Local hyperthermia treatment of tumors induces CD8(+) T cell-mediated resistance against distal and secondary tumors.
abstract: Combinatorial use of iron oxide nanoparticles (IONPs) and an alternating magnetic field (AMF) can induce local hyperthermia in tumors in a controlled and uniform manner. Heating B16 primary tumors at 43°C for 30 min activated dendritic cells (DCs) and subsequently CD8(+) T cells in the draining lymph node (dLN) and conferred resistance against rechallenge with B16 (but not unrelated Lewis Lung carcinoma) given 7 days post hyperthermia on both the primary tumor side and the contralateral side in a CD8(+) T cell-dependent manner. Mice with heated primary tumors also resisted rechallenge given 30 days post hyperthermia. Mice with larger heated primary tumors had greater resistance to secondary tumors. No rechallenge resistance occurred when tumors were heated at 45°C. Our results demonstrate the promising potential of local hyperthermia treatment applied to identified tumors in inducing anti-tumor immune responses that reduce the risk of recurrence and metastasis.
  
  
  BACKGROUND
  Local heating of tumors via iron oxide NPs and an alternating magnetic field led to activation of anti-cancer CD8 T cells, which resulted in resistance against re-challenge and greater resistance to secondary tumors. Similar local heating-based strategies may become an important weapon in enhancing tumor elimination via a naturally existing but attenuated immune response.
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755.
authors.forename: Seiko
authors.initials: S
authors.lastname: Toraya-Brown
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755.
authors.forename: Mee Rie
authors.initials: MR
authors.lastname: Sheen
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755.
authors.forename: Peisheng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Baird
authors.affiliation: Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH03755.
authors.forename: Eugene
authors.initials: E
authors.lastname: Demidenko
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755.|Norris Cotton Cancer Center, Lebanon, NH 03756.
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: Turk
authors.affiliation: Department of Surgery, Geisel School of Medicine at Dartmouth, Hanover, NH 03755.|Thayer School of Engineering, Dartmouth College, Hanover, NH 03755.|Norris Cotton Cancer Center, Lebanon, NH 03756.
authors.forename: P Jack
authors.initials: PJ
authors.lastname: Hoopes
authors.affiliation: Tumor Microenvironment and Metastasis Program, the Wistar Institute, Philadelphia, PA 19104.
authors.forename: Jose R
authors.initials: JR
authors.lastname: Conejo-Garcia
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755.|Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, NH 03755.|Norris Cotton Cancer Center, Lebanon, NH 03756.
authors.forename: Steven
authors.initials: S
authors.lastname: Fiering
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D006979:Hyperthermia, Induced / Q000379:methods*; D060526:Magnetic Fields; D058185:Magnetite Nanoparticles / Q000627:therapeutic use*; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*
chemical_list: D058185:Magnetite Nanoparticles
keywords: Anti-tumor immune; Heat; Iron oxide; Local hyperthermia; Nanoparticle