The peripheral myeloid expansion driven by murine cancer progression is reversed by radiation therapy of the tumor.
Expansion of myeloid-lineage leukocytes in tumor-bearing mice has been proposed as a cause of systemic immunosuppression. We demonstrate that radiation therapy of tumors leads to a decline in myeloid cell numbers in the blood and a decrease in spleen size. The frequency of myeloid cells does not decline to the level seen in tumor-free mice: we demonstrate that metastatic disease can prevent myeloid cell numbers from returning to baseline, and that tumor recurrence from residual disease correlates with re-expansion of myeloid lineage cells. Radiation therapy results in increased proliferation of T cells in the spleen and while T cell responses to foreign antigens are not altered by tumor burden or myeloid cell expansion, responses to tumor-associated antigens are increased after radiation therapy. These data demonstrate that myeloid cell numbers are directly linked to primary tumor burden, that this population contracts following radiation therapy, and that radiation therapy may open a therapeutic window for immunotherapy of residual disease.
Earle A Chiles Research Institute, Robert W Franz Cancer Center, Providence Portland Medical Center, Portland, Oregon, United States of America.
Marka R
MR
Crittenden
Talicia
T
Savage
Benjamin
B
Cottam
Keith S
KS
Bahjat
William L
WL
Redmond
Shelly
S
Bambina
Melissa
M
Kasiewicz
Pippa
P
Newell
Andrew M
AM
Jackson
Michael J
MJ
Gough
D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy*; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D002452:Cell Count; D049109:Cell Proliferation; D005260:Female; D005720:Gamma Rays / Q000627:therapeutic use*; D007108:Immune Tolerance; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy*; D051379:Mice; D022423:Myeloid Cells / Q000276:immunology / Q000473:pathology / Q000528:radiation effects*; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy*; D012867:Skin; D013154:Spleen / Q000276:immunology / Q000473:pathology / Q000528:radiation effects; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000528:radiation effects*; D016042:Transplantation, Heterotopic; D047368:Tumor Burden / Q000528:radiation effects*
D000951:Antigens, Neoplasm