Abstract 79: Immunomodulation in response to radiation-induced lung injury.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Introduction. Pneumonitis and fibrosis constitute dose-limiting side effects of thorax and whole body irradiation. Although several novel disease biomarkers have been described during recent years, the cellular and molecular factors responsible for disease initiation and progression are still not sufficiently understood. Here, we characterized local and systemic changes in the immune cell compartment in response to radiation-induced lung injury and defined the role of lymphocytes for fibrosis development in a murine model. Material and methods A single dose of hemithorax or whole thorax irradiation (15 Gy) was applied on C57BL/6 wild type mice (WT) or immunodeficient RAG-2-/- mice. Mice were sacrificed at defined time points and lungs were isolated for histological and immunohistochemical analysis as well as immune cell phenotyping. Moreover, immune cells were isolated from spleen, blood and cervical lymph nodes and also characterized by flow cytometry. Bronchioalveolar lavage fluid was collected for determination of cytokine levels. Results and discussion. Whole thorax irradiation triggered time-dependent changes in the composition and activation state of immune cells isolated from the lung tissue. These changes were paralleled by specific alterations in the cytokines present in the bronchoalveolar lavage fluid. In WT mice whole thorax irradiation with 15 Gy led to a time-dependent increase in collagen deposition and lung fibrosis. Irradiated RAG-2-/- mice showed an earlier onset of collagen deposition and an increased number of fibrotic foci in the lung when compared to WT mice. Conclusion. Thorax irradiation triggers local and systemic changes in the composition and the activation state of immune cells. The increased sensitivity of RAG-2-/- mice to radiation-induced fibrosis suggests a role of mature lymphocytes in the suppression of fibrotic changes. An improved understanding of the contribution of specific immune cells to the pathogenic process in the lung may open novel routes to prevent or treat radiation-induced pneumopathy. Citation Format: Federica Cappuccini, Florian Wirsdorfer, Malagorzata Drabczyk, Therese Eldh, Ali Sak, Verena Jendrossek. Immunomodulation in response to radiation-induced lung injury. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 79. doi:10.1158/1538-7445.AM2013-79