Background Recently, immunologic responses to localized irradiation are proposed as mediator of systemic effects after localized radiotherapy (called the abscopal effect). Here, we give an overview of both preclinical and clinical data about the abscopal effect in particular and link them with the immunogenic properties of radiotherapy. Methods We searched Medline and Embase with the search term “abscopal” from 1960 until July, 2014. Only papers that cover radiotherapy in an oncological setting were selected and only if no concurrent cytotoxic treatment was given. Targeted immune therapy was allowed. Results Twenty-three case reports, one retrospective study and 13 preclinical papers were selected. Eleven preclinical papers used a combination of immune modification and radiotherapy to achieve abscopal effects. Patient age range (28 to 83 years) and radiation dose (median total dose 32 Gy) varied. Fractionation size ranged from 1,2 Gy to 26 Gy. Time to documented abscopal response ranged between less than one and 24 months, with a median reported time of 5 months. Once an abscopal response was achieved, a median time of 13 months went by before disease progression occurred or the reported follow-up ended (range 3–39 months). Conclusion Preclinical data points heavily towards a strong synergy between radiotherapy and immune treatments. Recent case reports already illustrate that such a systemic effect of radiotherapy is possible when enhanced by targeted immune treatments. However, several issues concerning dosage, timing, patient selection and toxicity need to be resolved before the abscopal effect can become clinically relevant.

Radiotherapy (RT) and chemotherapy can induce immune responses, but not much is known regarding treatment-induced immune changes in patients. This exploratory study aimed to identify potential prognostic and predictive immune-related proteins associated with progression-free survival (PFS) in patients with non-small cell lung cancer (NSCLC). In this prospective study, patients with stage I NSCLC treated with stereotactic body radiation therapy (n = 26) and patients with stage III NSCLC treated with concurrent chemoradiotherapy (n = 18) were included. Blood samples were collected before (v1), during (v2), and after RT (v3). In patients with stage I NSCLC, CD244 (HR: 10.2, 95% CI: 1.8–57.4) was identified as a negative prognostic biomarker. In patients with stage III NSCLC, CR2 and IFNGR2 were identified as positive prognostic biomarkers (CR2, HR: 0.00, 95% CI: 0.00–0.12; IFNGR2, HR: 0.04, 95% CI: 0.00–0.46). In addition, analysis of the treatment-induced changes of circulating protein levels over time (Δv2/v3−v1) also identified CXCL10 and IL-10 as negative predictive biomarkers (CXCL10, HR: 3.86, 95% CI: 1.0–14.7; IL-10, HR: 16.92 (2.74–104.36)), although serum-induced interferon (IFN) response was a positive prognostic. In conclusion, we identified several circulating immunogenic proteins that are correlated with PFS in patients with stage I and stage III NSCLC before and during treatment.

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