Abstract 1767: Peripheral blood neutrophil-to-lymphocyte ratio (NLR), a predictor of poor survival in cancer patients, was positively associated with the percentage of circulating low-density neutrophil fraction
Authors: Rohanizadeh Ramin , Koufos Olivia , Su Xin , Brassard Ariane , Giannias Betty , Bourdeau France , Rayes Roni , Spicer Jonathan , Sangwan Veena , Bailey Swneke , Ferri Lorenzo , Cools-Lartigue Jonathan 
Published: July 2021

Low density (LDNs) and high density (HDNs) are two neutrophil subsets that can be separated through gradient centrifugation. LDNs was shown to be a tumor-promoting phenotype and high percentage of circulating LDNs was associated with poor cancer prognosis. In the last decade, it has also been suggested that neutrophil-to-lymphocyte ratio (NLR) is a marker of cancer-associated inflammation and high peripheral blood NLR was associated with poor cancer patient survival. Our study therefore aimed to i) establish the correlation between the percentage of circulating LDN fraction and blood NLR in cancer patients; ii) determine the differences between LDN and HDN protein expression; iii) compare the protein expression of neutrophils between cancer patients and healthy volunteers.

Materials & methods: Peripheral blood of esophageal/gastric cancer patients with clinical stage of II-III were collected. Circulating LDNs and HDNs were isolated using differential density centrifugation, and protein expression determined by immunophenotyping of cells using 12 different markers. Immunophenotyping of neutrophils from healthy volunteers was compared with that of cancer patients using the same panel of markers.

Results: The percentage of circulating LDN fraction varied between 0.2% to 40% in cancer patients with an average higher than that in healthy volunteers. LDN fraction was significantly elevated in patients with high peripheral blood NLR (NLR above 4). We observed a positive Pearson's correlation between NLR and LDN fraction in blood of cancer patients. Compared to HDNs, pro-tumor LDNs was bigger in size and exhibited a higher expression of Arginase 1 (Arg1), CD66b (CEACA-8), and CXCR2. Peripheral blood neutrophils (PBNs) in cancer patients, containing both HDN and LDN fractions, showed a lower expression of Arg1 and neutrophil elastase (NE).

Conclusion: Higher percentage of circulating LDNs in patients with elevated blood NLR may explain the correlation between high NLR and poor survival in cancer patients. High Arg1 expression of LDNs compared to HDNs can contribute to LDNs pro-tumor activity. Decreased expression of Arg1 and NE in PBNs of cancer patients compared to healthy subjects could be due to the degranulation of PBNs in cancer patients.

Citation Format: Ramin Rohanizadeh, Olivia Koufos, Xin Su, Ariane Brassard, Betty Giannias, France Bourdeau, Roni Rayes, Jonathan Spicer, Veena Sangwan, Swneke Bailey, Lorenzo Ferri, Jonathan Cools-Lartigue. Peripheral blood neutrophil-to-lymphocyte ratio (NLR), a predictor of poor survival in cancer patients, was positively associated with the percentage of circulating low-density neutrophil fraction [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1767.