Fractionated Radiation Severely Reduces the Number of CD8+ T Cells and Mature Antigen Presenting Cells Within Lung Tumors
Autor: | Thierry Gevaert, Pieterjan Debie, Hanne Locy, Eva Reijmen, Sandrina Martens, Cleo Goyvaerts, Kirsten De Ridder, Sven De Mey, Luc Bouwens, Jacques De Greve, Wout De Mey, Emmy De Blay, Karine Breckpot, Mark De Ridder |
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Přispěvatelé: | Laboratory of Molecullar and Cellular Therapy, Basic (bio-) Medical Sciences, Faculty of Medicine and Pharmacy, Clinical sciences, Radiation Therapy, Experimental Pathology, Laboratory for Medical and Molecular Oncology, Cell Differentiation, Medical Imaging, Medical Genetics, Translational Radiation Oncology and Physics, Laboratory of Molecular and Medical Oncology |
Rok vydání: | 2020 |
Předmět: |
Cancer Research
Lung Neoplasms T cell medicine.medical_treatment Antigen-Presenting Cells CD8-Positive T-Lymphocytes radiation therapy 030218 nuclear medicine & medical imaging 03 medical and health sciences Mice 0302 clinical medicine medicine Cytotoxic T cell Animals Radiology Nuclear Medicine and imaging Antigen-presenting cell Lung cancer CD86 Radiation business.industry Lewis lung carcinoma Immunotherapy medicine.disease Mice Inbred C57BL lung cancer medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cancer research Female Dose Fractionation Radiation business CD8 |
Zdroj: | International journal of radiation oncology, biology, physics. 111(1) |
ISSN: | 1879-355X |
Popis: | Purpose The combination of standard-of-care radiation therapy (RT) with immunotherapy is moving to the mainstream of non-small cell lung cancer treatment. Multiple preclinical studies reported on the CD8+ T cell stimulating properties of RT, resulting in abscopal therapeutic effects. A literature search demonstrates that most preclinical lung cancer studies applied subcutaneous lung tumor models. Hence, in-depth immunologic evaluation of clinically relevant RT in orthotopic lung cancer models is lacking. Methods and Materials We studied the therapeutic and immunologic effects of low-dose fractionated RT on lungs from C57BL/6 mice, challenged 2 weeks before with firefly luciferase expressing Lewis lung carcinoma cells via the tail vein. Low-dose fractionation was represented by 4 consecutive daily fractions of image guided RT at 3.2 Gy. Results We showed reduced lung tumor growth upon irradiation using in vivo bioluminescence imaging and immunohistochemistry. Moreover, significant immunologic RT-induced changes were observed in irradiated lungs and in the periphery (spleen and blood). First, a significant decrease in the number of CD8+ T cells and trends toward more CD4+ and regulatory T cells were seen after RT in all evaluated tissues. Notably, only in the periphery did the remaining CD8+ T cells show a more activated phenotype. In addition, a significant expansion of neutrophils and monocytes was observed upon RT locally and systemically. Locally, RT increased the influx of tumor-associated macrophages and conventional type 2 dendritic cells, whereas the alveolar macrophages and conventional type 1 DCs dramatically decreased. Functionally, these antigen-presenting cells severely reduced their CD86 expression, suggesting a reduced capacity to induce potent immunity. Conclusions Our results imply that low-dose fractionated RT of tumor-bearing lung tissue shifts the immune cell balance toward an immature myeloid cell dominating profile. These data argue for myeloid cell repolarizing strategies to enhance the abscopal effects in patients with non-small cell lung cancer treated with fractionated RT. |
Databáze: | OpenAIRE |
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