Background: Recently, the tumor immune environment has been found to play an intricate role in lung cancer progression. Studies have demonstrated that cancer cells can attract neutrophils into the tumor stroma through precise chemokine signaling pathways. Consequently, neutrophils promote angiogenesis, metastasis and inhibit apoptosis, whereas lymphocytes assist with tumor defense. Increased peritumoral neutrophil-tolymphocyte ratio (NLR) has been shown to mediate T cell anergy and tumor immune evasion. Elevated blood NLR has been shown to correlate with increased tumor neutrophil infiltration and decreased CD3(+) T-cell infiltration in various solid tumor pre-clinical models. Immune checkpoint inhibitors, which harness endogenous lymphocytic response to fight cancer, have recently emerged as the most promising anticancer therapies in Non-Small Cell Lung Cancer (NSCLC). We hypothesized that peripheral blood NLR could be a predictive marker for clinical benefit from immune checkpoint inhibition. Methods: We performed a single institution retrospective analysis of 50 patients with NSCLC treated with Nivolumab from July 2015 to April of 2016. Each patient's NLR was evaluated prior to starting therapy with Nivolumab. A cut-off of 5 was used to classify NLR as high or low based on prior studies. The presence or absence of clinical benefit to therapy was determined. Clinical benefit was defined as objective response or stable disease as per RECIST criteria after at least 3 months of therapy. Descriptive statistics were utilized to summarize the data. Chi-square test was used to compare clinical benefit from Nivolumab in low and high NLR populations. Results: There were 48 evaluable patients. 32 patients (66.7%) had a low pre-Nivolumab NLR. 24 (75%) of these patients were noted to have a clinical benefit at 3 months of Nivolumab treatment.16 patients (33.3%) of patients had a high NLR, of whom only 3 patients experienced a clinical benefit (18%). This difference was statistically significant (P=0.05). 2 patients with low NLR were lost to follow up and were not included in the analysis. Conclusion: The immune response to cancer is lymphocyte dependent. Lymphopenia, or neutrophilia, resulting in a high NLR may predict for a lack of clinical benefit from Nivolumab. In our study, the majority of patients with low pre-treatment NLR experienced clinical benefit from Nivolumab whereas most of the patients with elevated NLR did not achieve a clinical benefit. Our data suggests that NLR as a predictive biomarker for clinical benefit from immune checkpoint inhibitors should be further investigated in large prospective studies.
Preeshagul, I., Sullivan, K., Paul, D., & Seetharamu, N. (2017). P3.02c-078 The Utilization of Pre-Treatment Neutrophil to Lymphocyte Ratio as a Predictive Marker for Efficacy of Immunotherapy in Non-Small Cell Lung Cancer. Journal of Thoracic Oncology, 12(1), S1325. https://doi.org/10.1016/j.jtho.2016.11.1874