Combining radiation plus immunotherapy to improve systemic immune response

Abstract

Over the past decade, the fields of oncology have made great strides in therapies. The development of new therapeutics and increased understanding of the role of the immune system in the development and treatment of cancer has led to increased collaboration between oncologic fields. Recent technologic advancements in radiation therapy (RT), including stereotactic beam radiation therapy (SBRT), have improved local control and offer an alternative to surgery for the control of oligometastatic disease. Immunotherapy has proven a promising therapeutic in the treatment of metastatic disease but treatment resistance remains a significant obstacle in the majority of patients. Together, radiation and immunotherapy offer potential to eliminate metastatic disease, reduce time to recurrence and improve overall survival. Major obstacles to these positive outcomes include high tumor burden, intratumoral heterogeneity, and the negative effects of tumor stroma, to name a few. Multimodality treatments are under heavy investigation. Promising data from clinical trials is emerging to highlight the value of RT in combination with immunotherapy. However, the mechanisms behind their synergistic effects remain to be fully elucidated. This review aims to highlight the existing literature and offers hypotheses to explain mechanisms behind the synergy of RT and immunotherapy.

Low-dose radiation treatment enhances systemic antitumor immune responses by overcoming the inhibitory stroma

“…However, radiation is also known to have a wide variety of immunomodulatory effects, and as such its potential for overcoming treatment resistance or improving the effectiveness of systemic therapies—particularly immunotherapy—is increasingly being recognized. 1 2 Indeed, high-dose stereotactic XRT (H-XRT) has been used in attempts to transform tumors into in situ vaccines by eliciting the release of neoantigens from the tumor that in turn prime T cells and contribute to T cell repertoire diversity. 3 Others have found that H-XRT in combination with anti-cytotoxic T-lymphocyte associated protein 4 (CTLA-4) can have a significant survival advantage in a murine 4T1 metastatic breast cancer model.…”

Prior or concurrent radiotherapy and nivolumab immunotherapy in non–small cell lung cancer

“…Only two patient received intracranial stereotactic radiotherapy and no patients received extracranial stereotactic radiotherapy. Further data on concurrent immunotherapy and RT are anticipated with numerous trials ongoing worldwide . It should be noted, this study did not analyze the precise timing of RT with respect to the date of nivolumab administration and hence does not provide information on whether nivolumab administration was delayed for RT.…”

Three discipline collaborative radiation therapy (3DCRT) special debate: I would treat all early‐stage NSCLC patients with SBRT

“…Yet, the 4.9% incidence of mediastinal recurrence was lower than that would be expected historically, raising the hypothesis of distant immune effects with the use of SBRT. Indeed, the possibility of tumor antigen presentation with ablative treatments and its impact on immunotherapeutic treatments is yet to be fully explored, and there are ongoing clinical trials combining SBRT with immunotherapy in lung cancer …”