Multidisciplinary therapy provided concurrently, sequentially, or in a response-adapted stepwise manner is routinely utilized in the current treatment paradigm of lung cancer [1], [2]. More than 50% of cancer patients receive radiation therapy (RT) to cure or alleviate their symptoms. Given its direct cytotoxic effects on malignant cells, RT to the thoracic region is an integral treatment modality for cancers of the lung, esophagus, or breast and Hodgkin lymphoma, which injuries surrounding healthy tissues and reprograms the tumor immune microenvironment [3].

Advances in the precise delivery of tRT, in combination with immunotherapy and/or chemotherapy, have improved the survival of lung cancer patients. Unfortunately, side effects from these combined therapies are concerning for increased risks of morbidity and mortality. Although it is generally known that RT can elicit immunological effects that are either stimulatory or suppressive to trigger anti-tumor T cell responses [3], the complicated mechanisms behind the chronic inflammation that is linked to RT-induced immune-related toxicities remain poorly understood. Increased clinical use of immune checkpoint inhibitors in combination with tRT presents an urgent need for us to understand the mechanisms behind tRT-induced toxicity in healthy tissue. Ionizing radiation during radiotherapy is known to induce an intense inflammatory response via alterations in cytokine gene expression in the TME of various cancers [4]. It is known that radiation induces IL-17 secretion by Foxp3+Treg cells in TME of diffuse large B-cell lymphoma (DLBCL) via IL-6, however, this is further elusive in the case of lung cancer [5]. Furthermore, IL-17 is very likely to interact with and influence other signaling axes, which could further relate to inflammation or immunological modulation in TME. Notedly, the protective or detrimental response of IL-17 expression upon radiation is dependent on the tissue type, microenvironment, and the precipitating trigger Overall, it is worth investigating the complex relationship between irradiation, inflammation, and respective immune response in specific tumor types. IL-17A is the most well-known member of a multifunctional cytokine family consisting of six members (IL-17A - F). IL-17 activity is transiently and moderately localized in barrier surface tissues in healthy persons to promote host defense and tissue healing [6]. Chronic stimulation or amplification of the IL-17 response can redirect antimicrobial and repair functions toward pathogenic inflammation and tissue remodeling. These processes can lead to tissue injury, tumorigenesis, chronic respiratory diseases, and autoimmune disorders [7], [8].

IL-17 and cells that produce IL-17, such as T helper17 (TH17) are frequently seen in the microenvironment of many cancers, however, it is yet unclear how these cells play a role in carcinogenesis [9]. However, the blocking of IL-17A is reported to improve the efficacy of anti-PD-1 immunotherapy in microsatellite stable colorectal cancer mouse models, the role of IL-17 is remained elusive in lung cancer [10]. It is still believed that the immunological environment and type of tumor would influence IL-17's role in carcinogenesis. Here, we summarize the findings of IL-17 in damaged tissue after tRT, inflammation, and lung cancer development.