Role of novel immunosuppressive CD10+ antigen-presenting neutrophils in promoting HCC tumorgenesis

Abstract

Introduction: High circulating neutrophil-to-lymphocyte ratio is a biomarker of poor clinical outcome in HCC and various cancers. Neutrophils have long been considered as key components in the innate immune system. Recent evidence has shown GM-CSF is highly expressed in the peritumoral area of HCC and can induce expression of MHC-II (HLA-DR) on polymorphonuclear neutrophils. However, limited findings are available on both the immunological roles of the cytokine and its activated neutrophil sub-population in HCC. Based on our preliminary findings, we hypothesized the novel antigen-presenting phenotype of neutrophils (defined as CD66b+ HLA-DR+) have a pivotal role in HCC tumorigenesis. Methods: The expression of CD66b and HLA-DR in 45 HCC clinical specimens were quantified using quantitative PCR. Immunohistochemistry and flow cytometry were used to confirm the presence of CD66b+ HLA-DR+ neutrophil subpopulation. Results: Our qPCR data showed that CD66b, HLA-DR, CD10 mRNA level were elevated in peritumoural areas of HCC patients, and significantly correlated with each other (p< 0.001) (Fig.1). Consistent findings were confirmed in immunohistochemistry and flow cytometry(Fig 2). Clinical analysis also demonstrated that CD66b+ HLA-DR+ CD10+ neutrophils significantly correlated with tumour size, recurrence, staging, venous infiltration (Fig. 3) and negatively correlated with disease-free survival and overall survival of HCC patients (p< 0.05). Conclusion: The results collectively indicated the novel tumour promoting roles of CD66b+ HLA-DR+ CD10+ neutrophils in HCC patients. Targeting such population may represent a potential therapeutic strategy.