Association of preoperative neutrophil-to-lymphocyte ratio with immune populations in the tumor microenvironment of patients with clear cell renal cell carcinoma.

Abstract

688 Background: Currently, there are no blood biomarkers that reflect the composition of immune cells in the tumor microenvironment (TME) of patients with clear cell renal cell carcinoma (ccRCC). High pre-operative neutrophil-to-lymphocyte ratio (NLR) is associated with adverse oncologic outcomes in ccRCC. However, how NLR relates to the immune cell composition in the TME is not well understood. Methods: We performed flow cytometry on tumor and adjacent normal renal tissue from a prospective cohort of patients who underwent surgery from 6/2015-7/2017. Immune cell populations, as a percent of total CD45+, were compared to baseline age, sex, body mass index (BMI), SSIGN score, sarcomatoid differentiation, and AJCC stage (I-IV). NLR was calculated using pre-operative absolute neutrophil-to-lymphocyte counts and further categorized as inflamed if NLR was ≥ 3. Correlations between continuous variables were performed using Spearman’s rank correlation. Comparisons of means were made using the Wilcoxon signed-rank test. Results: Among 48 patients, 32 (71%) were male, median age was 59 (IQR 52-66), BMI of 38.5 (IQR 26-32.6), SSIGN score of 8 (IQR 5-12), 9 (20%) had sarcomatoid differentiation, and 20 (44%) had metastases at presentation. No correlations were found between age, BMI, and different immune cell populations or NLR. A higher ratio of tissue resident (CD8a+CD49a+CD103+) to circulating (CD8a+CD49a-CD103-) CD8+ T-cells in the TME was associated with increasing stage at presentation (p = 0.02). Inflamed patients had similar total CD45+, CD8+ T cell, CD4+ T cell, and macrophage immune infiltration. However, inflamed patients had a higher proportion of CD8+ Tres infiltration (p = 0.04) and a trend towards higher neutrophil infiltration (p = 0.15). Conclusions: A higher proportion of resident CD8+T-cells correlated with advanced disease at presentation. NLR may reflect a change in the type of CD8+T cell population found in the TME. This population of CD8+ T-cells, and NLR as a possible biomarker should be validated and further investigated in a larger cohort of patients. Funding: Ruth L. Kirschstein Research Service Award T32CA082088 (A.S., M.G.)