4.6 Article

Local hyperthermia treatment of tumors induces CD8+ T cell-mediated resistance against distal and secondary tumors

Journal

NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 10, Issue 6, Pages 1273-1285

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2014.01.011

Keywords

Iron oxide; Nanoparticle; Local hyperthermia; Heat; Anti-tumor immune

Funding

  1. Dartmouth Center of Nanotechnology Excellence National Institutes of Health [1 U54 CA151662]
  2. Center for Molecular, Cellular, and Translational Immunological Research NIGMS [P20 RR15639]
  3. Norris Cotton Cancer Support Grant [P30 CA023108]
  4. Dartmouth Immunobiology of Myeloid and Lymphoid Cells [5T32AI007363-22]

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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 degrees 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 degrees 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. (C) 2014 Elsevier Inc. All rights reserved.

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