Neutrophil to lymphocyte ratio (NLR), a broad measure of inflammation and immune function, predicts outcome including overall survival (OS) in aCRC but the underlying mechanisms are unclear. Better understanding of IR in these patients may identify potential responders to novel immunotherapy. We investigated whether immune function correlated to NLR and how this altered during chemotherapy.
Peripheral blood was taken from 29 aCRC patients receiving 1st line chemotherapy (baseline and 6 weeks). NLR of ≥ 5 was defined as high. Immune function of peripheral blood mononuclear cells (PBMCs) was determined by NK cell activity (degranulation by CD107 expression and cytotoxic potential by 51Chromium release) against target tumour cells, T cell activity by IFN-γ ELISpot, cytokine secretion (Luminex) and immune cell activation (flow cytometry).
High baseline NLR was associated with shorter OS compared to low NLR (6.6 vs. 18.8 months; HR = 3.6 [1.25 to 10.35] p = 0.0024). High NLR also correlated with a depressed IR, including decreased cytolytic activity of PBMCs (p = 0.046), NK cell degranulation at baseline and decreased levels of certain immune stimulatory cytokines. Low baseline NLR correlated with increased T cell activity against tumour-associated carcinoembryonic antigen (CEA) after 6 weeks of chemotherapy. Higher cytotoxic activity of PBMCs against target tumour cells at baseline (seen in the majority of patients with NLR
This study supports the poor prognosis of a high baseline NLR in aCRC and demonstrates its association with an attenuated IR. Chemotherapy can partially reverse this phenomenon, potentially enhancing anti-tumour immunity. If chemotherapy leads to a more effective anti-tumour IR, sequential immunotherapy could exploit this.
Clinical trial identification
Legal entity responsible for the study
University of Leeds
Cancer Research UK, Yorkshire Cancer Research
All authors have declared no conflicts of interest.