Abstract
Leukocytosis is a common feature of malignancies. While controversial, there appears to be an association between the degree of tumor-related leukocytosis and prognosis. In this paper, we provide evidence supporting an untapped clinical paradigm linking G-CSF secretion to the induction of leukocytosis and expansion of myeloid-derived suppressor cells, providing an explanation for the association between leukocytosis, elevated neutrophil-to-lymphocyte ratios and prognosis in non-small cell lung cancer. Clinically validating this mechanism may identify MDSCs and G-CSF as dynamic markers of early disease progression and therapeutic response, and shed light onto novel therapeutic avenues for the treatment of patients with non-small cell lung cancer.
Highlights
Leukemoid reactions are defined by the presence of white counts of >50 k/μl, and are considered paraneoplastic when other causes have been excluded
We provide evidence supporting an untapped clinical paradigm linking granulocyte-colony stimulating factor (G-CSF) secretion to the induction of leukocytosis and expansion of myeloid-derived suppressor cells, providing an explanation for the association between leukocytosis, elevated neutrophil-to-lymphocyte ratios and prognosis in non-small cell lung cancer
We performed an extensive review of the literature and propose a novel mechanism by which leukocytosis and G-CSF production are likely linked to neutrophil-to-lymphocyte ratios (NLR), tumor progression, metastasis, and poorer outcomes via myeloid derived suppressor cell (MDSC) in patients with non-small cell lung cancer (NSCLC)
Summary
Leukemoid reactions are defined by the presence of white counts of >50 k/μl (normal range 4–11 k/μl), and are considered paraneoplastic when other causes have been excluded. Paraneoplastic leukemoid reactions (PLRs) are rare phenomena that are more commonly reported in case reports, whereas milder forms of leukocytosis are commonly observed in solid tumors [1]. Studies have shown that among patients with newly diagnosed lung cancer, 14.5% have leukocytosis, and ∼20% of those with leukocytosis have a solid malignancy [2]. While PLR is distinguished from milder forms of leukocytosis in the scientific literature, the two are likely part of a continuum defined by the degree of cytokine production, and are referred to as “tumor-related leukocytosis.”. We performed an extensive review of the literature and propose a novel mechanism by which leukocytosis and G-CSF production are likely linked to neutrophil-to-lymphocyte ratios (NLR), tumor progression, metastasis, and poorer outcomes via MDSCs in patients with non-small cell lung cancer (NSCLC)
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