Radiation, Inflammation, and Immune Responses in Cancer

Abstract

Chronic inflammation has emerged as one of the hallmarks of cancer. Inflammation also plays a pivotal role in modulating radiation responsiveness of tumors. As discussed in this review, ionizing radiation (IR) leads to activation of several transcription factors modulating the expression of numerous mediators in tumor cells and cells of the microenvironment promoting cancer development. Novel therapeutic approaches thus aim to interfere with the activity or expression of these factors, either in single-agent or combinatorial treatment or as supplements of the existing therapeutic concepts. Among them, NF-κB, STAT-3, and HIF-1 play a crucial role in radiation-induced inflammatory responses embedded in a complex inflammatory network. A great variety of classical or novel drugs including nutraceuticals such as plant phytochemicals have the capacity to interfere with the inflammatory network in cancer and are considered as putative radiosensitizers. Thus, targeting the inflammatory signaling pathways induced by IR offers the opportunity to improve the clinical outcome of radiation therapy by enhancing radiosensitivity and decreasing putative metabolic effects. Since inflammation and sex steroids also impact tumorigenesis, a therapeutic approach targeting glucocorticoid receptors and radiation-induced production of tumorigenic factors might be effective in sensitizing certain tumors to IR.

RIG-I–like receptor LGP2 protects tumor cells from ionizing radiation

“…This pathway is a subtype of pattern recognition receptors responsible for primary recognition of pathogen and host-associated molecular patterns and the subsequent activation of type I IFN production that orchestrates an innate immune response (22)(23)(24). In addition to its role in inhibiting IFNβ expression, Suthar et al recently demonstrated that LGP2 governs CD8+ T-cell fitness and survival by inhibiting death-receptor signaling (25).…”

Therapeutic efficacy of boron neutron capture therapy mediated by boron-rich liposomes for oral cancer in the hamster cheek pouch model

“…It is known that inflammation associated with mucositis can induce tumor promotion, activating premalignant lesions (36,44). It is one of the hallmarks of cancer, acting on any stage of tumorigenesis (45). Within this context, the fact that BNCT can be delivered without enhancing mucositis is not only an asset in terms of preventing toxicity but also in terms of inhibiting the development of novel tumors.…”

Neoadjuvant Radiotherapy of Early-Stage and Locally Advanced Breast Cancer: Review of the Literature

“…Cytokines are thought to elicit augmented tumor surveillance, inhibit tumor growth, and have direct tumoricidal properties [18]. Thus, it is believable that neoadjuvant radiation to the large bulk tumor can activate robust antitumor specific immune responses, which is absent after postoperative RT to the tumor bed, according to recent studies focused to relation between radiation and immune system [19,20]. This synergy stems come from the fact that RT potentially converting the tumor into a patient-specific in situ vaccine capable of re-educating the immune system to recognize and reject cancer [21,22].…”