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.