Neutrophil Lymphocyte Ratio as predictor of treatment response in malignancy

Cancer is a devastating disease characterized by uncontrolled division of cells. These cancerous cells have, through genetic mutations, acquired abnormal growth, increased survival, and often an ability to avoid detection by our immune system. However, sometimes, our immune system receives a faulty message and instead protects the cancer from being removed. One immune cell participating in protecting the tumor cell, in some circumstances, is the neutrophil, a type of white blood cell. Neutrophils not only produce proteins to promote tumor growth and metastasis, which is when cancer spreads to another part of the body, they also prevent killing of the cancer cell. Given their prominent role in malignancy (the presence of cancer) it has been proposed that monitoring neutrophils may provide insight into the disease progression.

Biomarkers, clinical markers that indicate a disease progression or a treatment response, give insight as to what is happening in a cell. The main neutrophil biomarker used to date is the neutrophil to lymphocyte ratio (NLR). Lymphocytes are another type of white blood cell that is part of the immune system. NLR has been shown to be an independent predictor of overall survival in metastatic castration-resistant prostate cancer (cancer that has spread beyond the prostate and for which hormone therapy is no longer effective in stopping the progression of the cancer). It has also been shown to be an independent predictor of overall survival in several other malignancies, primarily solid tumors. The thought is that a high NLR could indicate tumor-related neutrophilia, which is an abnormally high number of neutrophil cells in the blood, and is associated with reduced clinical efficacy of the drug. Ongoing studies in mice are currently exploring whether targeting neutrophils at the same time as giving chemotherapy is beneficial. Given the clinical significance of early treatment in malignancy to prevent metastasis and/or death, early and efficient treatment is essential. Thus, identifying biomarkers able to guide treatment, e.g. personalized treatment, is of uttermost important in these patients. In the current proposal, I will study lung cancer, colorectal cancer, and gastric cancer, accounting for more than a total of 400,000 cases (180,000 deaths) annually in the US.

The research will implicate neutrophils in cancer progression, promoting drug development to target neutrophil biology in cancer patients, as well as more immediately identify clinical markers of disease progression or treatment response that can assist in determining best treatment strategy for individual patients. One major benefit of this biomarker is its availability in a clinical setting, not requiring additional instrumentation.
In the current proposal, I will study lung cancer… annually in the US, to validate prior work on the ability of NLR to predict disease outcome, as well as to determine whether NLR can identify patients responding to select treatment.

In brief, I will investigate levels of NLR in six clinical trials at various stages of disease progression of lung cancer and gastric cancer, to determine i) the association of NLR with disease progression; ii) the ability of NLR to predict disease progression); and iii) the ability of NLR to predict treatment response. Main outcome markers will be to study overall survival and progression-free survival. This design will allow me to study various degrees of disease progression (to see whether NLR is associated with disease severity), compare two forms of solid tumors (lung vs gastric) as well as determine whether any of the treatment strategies are more or less dependent on NLR.

In brief, I hope to find a new marker that is easily accessible in clinical practice that can help guide clinicians in determining treatment options for patients to increase timely, and efficient treatment in patients with solid tumor.