The immune system is pivotal in mediating the anti-tumor effects of radiation therapy (46.3)
| Autor: | Scott Gerber, Abigail Sedlacek, Edith Lord |
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| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 188:46.3-46.3 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | A new paradigm has emerged demonstrating that the immune system mediates many of the anti-tumor effects of radiation therapy (RT). RT continues to be a cornerstone in the treatment for many cancers, unfortunately not all individuals respond effectively to RT resulting clinically into two groups consisting of non-responders (progressive disease) and partial/complete responders (tumor control/cure). We have designed a unique model that mirrors this clinically relevant phenomenon in which mice bearing colon38, a colon adenocarcinoma, were treated locally with 15Gy RT resulting in both non-responders and responders. Interestingly, our data uncovered a window of interest four days following RT in which critical events occurred that ultimately determined the effectiveness of therapy. Intratumoral IFNγ was increased in responsive tumors and licensed CD8 T cells to exhibit potent lytic activity against tumor cells; a response that was greatly diminished in tumors refractory to RT. We explored whether enhancing IFNγ and CD8 T cells via immunotherapy would increase the responder to non-responder ratio. Indeed, multi-modality therapy comprised of IL-12 and RT in mice bearing colon38 tumors resulted in complete remission of cancer in 100% of cases compared to a cure rate of only 40% with RT alone. Our data suggests that the efficacy of RT may depend on the immune response generated shortly after treatment and targeting this component may greatly enhance the effectiveness of RT. |
| Databáze: | OpenAIRE |
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