Systemic Leukocyte Alterations in Cancer and their Relation to Prognosis

Abstract

Leukocyte migration is a key event in the inflammatory response to tumors. The tumor releases specific chemokines that control migration of leukocytes and functions of these cells after their arrival at the tumor site. In addition to these local changes in the tumor microenvironment, the host response to malignant solid tumors also gives rise to systemic effects, the most frequent of which are leukocytosis, neutrophilia and lymphopenia. These hematological findings are significantly correlated with advanced tumor stage and, therefore, poor disease prognosis. The ratio of neutrophil and lymphocyte counts has been suggested as a simple parameter of systemic inflammation in cancer patients. An elevated neutrophil to lymphocyte ratio has been shown to be an independent prognostic factor for cancers at various different sites, suggesting that this parameter is a clinically accessible and useful biomarker for patient survival. The effect of tumor development on circulating leukocyte number has not been clarified. One proposed mechanism is that tumor cells produce soluble factors such as granulocyte colony stimulating factor, which mobilize precursor cells in the bone marrow, or other mediators that alter cell differentiation. Leukocyte counts may be readily obtained at the time of diagnosis, and these data could be useful as stratification factors in clinical trials and in identifying patients with poor prognosis, leading to better treatment strategies.