Radiation and immunotherapy: Renewed allies in the war on cancer

Abstract

Anticancer immunotherapy holds great promises, as long-term responses to interleukin-2 have been observed in metastatic melanoma and renal cell carcinoma patients. However, improving the relative low rates of such responses has constituted a great challenge. In our experience, high-dose radiation combined with interleukin-2 provided encouraging results that are worth exploring further.

Figure 1. Immunogenic effects of irradiation. Radiation-induced tumor cell death provides a source of tumor-associated antigens (TAAs), and increases the expression of MHC class I molecules, adhesion molecules, and a plethora of other factors involved in the immune response, including death receptors. In response to irradiation, cytokines and chemokines are released, in turn attracting antigen-presenting cells (APCs) and T cells. Radiation-treated tumor cells can passively release high mobility group box 1 (HMGB1) that, by binding to Toll-like receptors (TLRs) on the surface of APCs, stimulates TAA presentation to effector cells. APCs process dead tumor cells and carry TAAs into draining lymph nodes, where antigen presentation and T-cell stimulation occur. Activated effector cells, expanded by interleukin-2 (IL-2), eventually target both irradiated and non-irradiated tumor cells.