The effect of hypofractionated radiation and magnetic nanoparticle hyperthermia on tumor immunogenicity and overall treatment response

Conference Paper

It is now known that many tumors develop molecular signals (immune checkpoint modulators) that inhibit an effective tumor immune response. New information also suggest that even well-known cancer treatment modalities such as radiation and hyperthermia generate potentially beneficial immune responses that have been blocked or mitigated by such immune checkpoints, or similar molecules. The cancer therapy challenge is to; a) identify these treatment-based immune signals (proteins, antigens, etc.); b) the treatment doses or regimens that produce them; and c) the mechanisms that block or have the potential to promote them. The goal of this preliminary study, using the B6 mouse - B16 tumor model, clinically relevant radiation doses and fractionation schemes (including those used clinically in hypofractionated radiation therapy), magnetic nanoparticle hyperthermia (mNPH) and sophisticated protein, immune and tumor growth analysis techniques and modulators, is to determine the effect of specific radiation or hyperthermia alone and combined on overall treatment efficacy and immunologic response mechanisms. Preliminary analysis suggests that radiation dose (10 Gy vs. 2 Gy) significantly alters the mechanism of cell death (apoptosis vs. mitosis vs. necrosis) and the resulting immunogenicity. Our hypothesis and data suggest this difference is protein/antigen and immune recognition-based. Similarly, our evidence suggest that radiation doses larger than the conventional 2 Gy dose and specific hyperthermia doses and techniques (including mNP hyperthermia treatment) can be immunologically different, and potentially superior to, the radiation and heat therapy regimens that are typically used in research and clinical practice.

Full Text

Duke Authors

Cited Authors

  • Hoopes, PJ; Wagner, RJ; Song, A; Osterberg, B; Gladstone, DJ; Bursey, AA; Fiering, SN; Giustini, AJ

Published Date

  • 2017

Published In

Volume / Issue

  • 10066 /

Start / End Page

  • 100660D -

PubMed ID

  • 29515284

Pubmed Central ID

  • PMC5837053

International Standard Serial Number (ISSN)

  • 0277-786X

Digital Object Identifier (DOI)

  • 10.1117/12.2255981