title: Cancer immunotherapy: how low-level ionizing radiation can play a key role.
abstract: The cancer immunoediting hypothesis assumes that the immune system guards the host against the incipient cancer, but also "edits" the immunogenicity of surviving neoplastic cells and supports remodeling of tumor microenvironment towards an immunosuppressive and pro-neoplastic state. Local irradiation of tumors during standard radiotherapy, by killing neoplastic cells and generating inflammation, stimulates anti-cancer immunity and/or partially reverses cancer-promoting immunosuppression. These effects are induced by moderate (0.1-2.0 Gy) or high (>2 Gy) doses of ionizing radiation which can also harm normal tissues, impede immune functions, and increase the risk of secondary neoplasms. In contrast, such complications do not occur with exposures to low doses (≤0.1 Gy for acute irradiation or ≤0.1 mGy/min dose rate for chronic exposures) of low-LET ionizing radiation. Furthermore, considerable evidence indicates that such low-level radiation (LLR) exposures retard the development of neoplasms in humans and experimental animals. Here, we review immunosuppressive mechanisms induced by growing tumors as well as immunomodulatory effects of LLR evidently or likely associated with cancer-inhibiting outcomes of such exposures. We also offer suggestions how LLR may restore and/or stimulate effective anti-tumor immunity during the more advanced stages of carcinogenesis. We postulate that, based on epidemiological and experimental data amassed over the last few decades, whole- or half-body irradiations with LLR should be systematically examined for its potential to be a viable immunotherapeutic treatment option for patients with systemic cancer.
authors.affiliation: Department of Radiobiology and Radiation Protection, Military Institute of Hygiene and Epidemiology, 4 Kozielska St., 01-163, Warsaw, Poland. mjaniak@wihe.waw.pl.
authors.forename: Marek K
authors.initials: MK
authors.lastname: Janiak
authors.affiliation: Department of Radiobiology and Radiation Protection, Military Institute of Hygiene and Epidemiology, 4 Kozielska St., 01-163, Warsaw, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Wincenciak
authors.affiliation: Department of Radiobiology and Radiation Protection, Military Institute of Hygiene and Epidemiology, 4 Kozielska St., 01-163, Warsaw, Poland.
authors.forename: Aneta
authors.initials: A
authors.lastname: Cheda
authors.affiliation: Department of Radiobiology and Radiation Protection, Military Institute of Hygiene and Epidemiology, 4 Kozielska St., 01-163, Warsaw, Poland.
authors.forename: Ewa M
authors.initials: EM
authors.lastname: Nowosielska
authors.affiliation: Department of Environmental Health Sciences, School of Public Health and Health Sciences, Morrill I, N344, University of Massachusetts, Amherst, MA, 01003, USA.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Calabrese
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000276:immunology / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007107:Immune System / Q000276:immunology / Q000528:radiation effects*; D007108:Immune Tolerance / Q000528:radiation effects*; D007165:Immunosuppression Therapy / Q000379:methods*; D007249:Inflammation / Q000473:pathology; D051379:Mice; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology / Q000532:radiotherapy*; D051381:Rats; D059016:Tumor Microenvironment / Q000276:immunology / Q000528:radiation effects; D014916:Whole-Body Irradiation
keywords: Carcinogenesis; Immune suppression; Low-level radiation; Radio-immunotherapy