The diversity of circulating neutrophils in cancer

Neutrophils, the most abundant leukocyte in human circulation are being more and more recognized as part of the immune reaction to cancer. In the last years, the understanding that neutrophils possess a dual role in cancer development has emerged. During tumor progression the number of neutrophils increase, and their phenotype change. In advanced cancer, we can find several sub-populations of circulating neutrophils possessing different characteristics of maturity, tumor cytotoxicity and immune suppression. One important sub-population of circulating neutrophils is the granulocytic myeloid derived suppressor cells (G-MDSC). Differencing G-MDSC from other sub-populations of neutrophils in the circulation is a complex and controversial task, as there are no clear definitions of the differences between these granulocytic sub-populations. Herein we review the differences described thus far between G-MDSC and other circulating neutrophils. We then compare the morphology, surface markers, function and prognostic importance of the different tumor-related circulating neutrophils, as described by us and others, and discuss the possible relations between the different sub-populations, their source and fate. Lastly, we suggest a nomenclature to try and encompass the full range of circulating neutrophils in cancer.