Peripheral Blood Neutrophil Granulocytes from Patients with Head and Neck Squamous Cell Carcinoma Functionally Differ from Their Counterparts in Healthy Donors

Abstract

Solid tumors such as head and neck squamous cell carcinoma (UNSee) display an intense interaction between tumoral factors and the immune system. Functional modulation of tumor-infiltrating and peripheral blood immune cells plays an important role during tumor progression. In this pilot study we compared biological functions of polymorphonuclear granulocytes (PMN) from the peripheral blood of UNSee patients and healthy subjects. PMN were simultaneously isolated from the peripheral blood of UNSee patients and healthy donors for functional analysis (apoptosis, production of reactive oxygen species (ROS), cytokine release and immunophenotyping). PMN from UNSee patients showed a significantly lower inducible production of ROS (P = 0.02) and reduced spontaneous apoptosis (P = 0.008) compared with PMN from healthy donors. Under standard culture conditions, there was no significant difference regarding the release of inflammatory cytokines between PMN from UNSee patients and PMN from healthy donors. Confirming previous observations, serum concentrations of PMN-related cytokines were significantly higher in the peripheral blood of UNSee patients than in that of controls. Importantly, immunophenotyping revealed an increased number of immature PMN in PMN fractions isolated from UNSee patients. Peripheral blood PMN from UNSee patients and healthy donors show distinct functional differences. The presence of increased numbers of immature stages of PMN in UNSee patients may partly contribute to the changes observed. After recruitment to and infiltration of the tumor, PMN may be further modulated in the local tumor microenvironment. This pilot study justifies functional analyses of myeloid cells in larger cohorts of patients with UNSee.Cancer-related inflammation in solid tumors is associated with modulation of immune cells finally resulting in tumor progression (I). Head and neck squamous cell carcinoma (HNSCC) displays frequent infiltration by various immune effector cells and reciprocal interaction between tumor and immune cells. This interaction leads to an increased local and systemic expression of immune-modulating mediators, often resulting in immuno-suppression and the escape of the tumor from immune control (2). Accumulating evidence suggests that polymorphonuclear granulocytes (PMN, neutrophils) and other myeloid cells play an important tumor-promoting role during tumor progression (3-4). In the tumor host, tumor-derived factors modulate PMN functions: For instance, in bronchioalveolar carcinoma, production of antiapoptotic factors by the tumor

The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment

“…The neutrophils from HNSCC showed lower inducible production of ROS, reduced spontaneous apoptosis and increased number of immature neutrophils [374]. The serum concentration of neutrophil related cytokines was higher in HNSCC patients [374].…”

“…Studies on neutrophils from patients with head and neck squamous cell carcinoma (HNSCC) showed that these neutrophils differ from their counterparts in healthy donors [374]. The neutrophils from HNSCC showed lower inducible production of ROS, reduced spontaneous apoptosis and increased number of immature neutrophils [374].…”

“…The neutrophils from HNSCC showed lower inducible production of ROS, reduced spontaneous apoptosis and increased number of immature neutrophils [374]. The serum concentration of neutrophil related cytokines was higher in HNSCC patients [374]. HNSCC tissue exhibited considerable infiltration by neutrophils, and strong infiltration was associated with poorer survival in advanced diseases [157].…”

Neutrophil-rich Pulmonary Carcinoma: Clinicopathological Characteristics and Cytokine Expression and Their Relationship with Lymph Node Metastasis

“…The number of TINs has been shown to be a strong, independent prognostic factor for recurrence-free and overall survival in metastatic 2 and localized clear cell renal cell carcinoma 3 , and in head and neck squamous cell carcinoma 4 , and a high neutrophil count has been found to be associated with a favorable prognosis in gastric cancer 5 . In contrast, the number of TINs was found to correlate with a high tumor grade in human gliomas 6 and to be related to more aggressive types of pancreatic tumors 7 .…”

Calcium Ionophore A23187 and Compound 48/80 Induce PGD2 and Tryptase in Human Cord Blood-Derived Mast Cells: Lack of Effect of IL-18

“…Recent studies also demonstrate a convincing role for IL-18 in atopic responses, including atopic inflammatory diseases (46)(47)(48)(49)(50). Moreover, IL-18 directly stimulates basophils and mast cells to produce Th2 cytokines and histamine independently of IgE.…”