Radiotherapy promotes tumor-specific effector CD8+ T cells via dendritic cell activation.
Radiotherapy is an important treatment for cancer. The main mode of action is thought to be the irreversible damage to tumor cell DNA, but there is evidence that irradiation mobilizes tumor-specific immunity, and recent studies showed that the efficacy of high-dose radiotherapy depends on the presence of CD8(+) T cells. We show in this study that the efficacy of radiotherapy given as a single, high dose (10 Gy) crucially depends on dendritic cells and CD8(+) T cells, whereas CD4(+) T cells or macrophages are dispensable. We show that local high-dose irradiation results in activation of tumor-associated dendritic cells that in turn support tumor-specific effector CD8(+) T cells, thus identifying the mechanism that underlies radiotherapy-induced mobilization of tumor-specific immunity. We propose that in the absence of irradiation, the activation status of dendritic cells rather than the amount of tumor-derived Ag is the bottleneck, which precludes efficient anti-tumor immunity.
Department of Oncology, University Hospital Zurich, Zurich, Switzerland.
Anurag
A
Gupta
Hans Christian
HC
Probst
Van
V
Vuong
Alexandro
A
Landshammer
Sabine
S
Muth
Hideo
H
Yagita
Reto
R
Schwendener
Martin
M
Pruschy
Alexander
A
Knuth
Maries
M
van den Broek
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000528:radiation effects; D018827:Carcinoma, Lewis Lung / Q000276:immunology* / Q000473:pathology / Q000532:radiotherapy*; D002454:Cell Differentiation / Q000276:immunology* / Q000528:radiation effects; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology / Q000532:radiotherapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic