Oncology Central

A primer on combining radiation and immunotherapy

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Radiation therapy and immunotherapy in combination have the ability to achieve a synergistic therapeutic effect. Indeed, while the standard view of whole body radiation is as an immune system detriment, there is growing evidence of focal radiation toward the contrary, supporting the notion of a combination treatment. Ideally, immunotherapy could be utilized to thwart cancer’s dampening effect on the immune system.

An effective primary immune response would have obvious benefits for patients. Recent clinical trials have been developed to explore the feasibility of immunotherapy combined with radiation therapy. The treatments within each trial vary, but all combine a standard radiation therapy with an immunotherapy; for example, radiation therapy in addition to intratumoral dendritic cell injection.

Thus, radiation-driven immunotherapy (RDI) is an exciting area of research where evidence is accumulating suggesting this biological process may have important ramifications for the future of clinical radiotherapy. In patients undergoing radiation, the complex interplay of tumor cell death, antigen expression, inflammatory signals, and lymphocyte and dendritic cell activation presents a unique therapeutic opportunity. The whole therapeutic effect can exceed the sum of its parts and can present the potential for further improvement of immunotherapy effects arising from therapeutic tumor irradiation to generate immunologic-mediated, radiation-driven personalized systemic therapy or RDI.

A fundamental mechanism of tumor killing through radiotherapy is induction of DNA damage in the cancer cells. This view is not a complete picture of the time course of cellular events within the tumor. Indeed, there are associated changes in the microenvironment, tumor-associated endothelial cells, inflammatory infiltrates and in systemic responses to the tumor destruction. Areas of higher dose exposure inside the bulk of the tumor may have markedly different pathways to cell death, emphasizing necrosis mechanisms. The time course of changes of antigen expression during the cell-killing process and differences among radiotherapy techniques can be relevant [1].

Several events have been studied for their specific immunotherapy relevance, beyond the phenomenon of cells dying within the radiated tumor. Some of the downstream events relate to inflammation and clearance of antigens within the irradiated volume; those of most interest are those that influence acquisition of a more activated general or more activated tumor-specific phenotype. The most dramatic outcome is when a distant tumor mass regresses as a consequence of this, known as the abscopal effect.

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