Tumor-related
leukocytosis (TRL) is occasionally found in patients with nonhematopoietic
malignancies. We investigated the clinical implication of TRL and individualized treatment for TRL-positive
cervical cancer, as well as the underlying biological mechanism.
METHODS: RESULTS: TRL was statistically significantly associated with younger age (Wilcoxon rank sum test, P = .03), larger
tumor size (Wilcoxon rank sum test, P = .006), advanced clinical stage (χ(2) test, P = .01), and shorter overall survival (Cox proportional hazard modeling and Wald tests, P < .001). Among
cervical cancer patients, TRL was associated with upregulated
tumor G-CSF expression (χ(2) test, P < .001), elevated serum
G-CSF levels (Student t test, P = .03), larger spleens (Student t test, P = .045), and increased MDSC frequencies in the blood (Student t test, P < .001) compared with the TRL-negative patients. In vitro and in vivo experiments revealed that
tumor-derived
G-CSF was involved in the underlying causative mechanism of TRL and MDSCs induced by
tumor-derived
G-CSF are responsible for the rapidly progressive and radioresistant nature of TRL-positive
cervical cancer. The administration of anti-Gr-1
neutralizing antibody or the depletion of MDSCs by
splenectomy (n = 6 per group) inhibited
tumor growth and enhanced radiosensitivity in TRL-positive
cervical cancer xenografts (Wilcoxon rank sum test, P = .008 and P = .02, respectively).
CONCLUSIONS: