Flt3-ligand administration after radiation therapy prolongs survival in a murine model of metastatic lung cancer.
An ineffective tumor-specific immune response from inadequate/incompetent antigen presentation could contribute to the failure in tumor control and its dissemination. Dendritic cells (DCs) have been shown to present antigen from apoptotic cells. We hypothesized that Flt3-ligand (Flt3L) therapy, which expands DCs in vivo, in combination with local tumor radiotherapy (RT), should improve antigen presentation from dying, irradiated tumor cells. RT + Flt3L reduced pulmonary metastases in a murine model of Lewis lung carcinoma and significantly improved survival in C57Bl/6 mice with established footpad tumors. Mice treated with Flt3L alone showed delayed tumor growth but eventually succumbed to tumor progression. The combination therapy of RT + Flt3L failed to impact survival in immunodeficient athymic mice, implicating the role of T cells in prolonging survival. These results support an attractive strategy of sequential RT and immunotherapy with Flt3L to enhance tumor antigen presentation, which may produce therapeutic responses against disseminated cancer and improvement in survival.
Chakravarty
P K
PK
Department of Radiation Oncology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York 10461, USA.
Alfieri
A
A
Thomas
E K
EK
Beri
V
V
Tanaka
K E
KE
Vikram
B
B
Guha
C
C
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy*; D008297:Male; D008565:Membrane Proteins / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009368:Neoplasm Transplantation; D011859:Radiography
D000970:Antineoplastic Agents; D008565:Membrane Proteins; C084881:flt3 ligand protein