The role of tumor-associated neutrophils in the pathogenesis of recurrent respiratory papillomatosis

Abstract

Neutrophils are known to infiltrate various tumor tissues extensively and contribute to disease progression. However, the role of tumor-associated neutrophils in the pathogenesis of recurrent respiratory papillomatosis remains unclear. This study aimed to explore the prognostic significance of tumor-associated neutrophils and examine their role in the pathogenesis of recurrent respiratory papillomatosis. Immunohistochemistry was employed to assess the intensity of neutrophil infiltration in RRP tumor tissues. Multifactorial logistic regression analysis was conducted to evaluate the relationship between tumor-associated neutrophils and patient prognosis. Flow cytometry analysis was used to examine the phenotype of neutrophils. Additionally, coculture assays were performed with tumor-associated neutrophils and peripheral T cells to assess their functional interactions. Immunohistochemical analysis revealed that patients with recurrent respiratory papillomatosis exhibited significantly higher neutrophil densities within tumor tissues. Elevated neutrophil counts, neutrophil-to-lymphocyte ratio, and tumor-associated neutrophil infiltration were observed in patients with more aggressive forms of recurrent respiratory papillomatosis. Multivariate logistic regression identified the extent of neutrophil infiltration as an independent risk factor for an aggressive clinical course in these patients. Furthermore, tumor-associated neutrophils expressed high levels of CXCR1, CXCR2, and arginase 1, indicating a protumor phenotype, along with elevated levels of PD-L1, an immunosuppressive molecule. Functionally, these tumor-associated neutrophils effectively suppressed T-cell proliferation, activation, and cytokine secretion. Thus, tumor-associated neutrophils play a crucial role in fostering an immunosuppressive microenvironment that enables tumor immune evasion. This process initiates a positive feedback loop, where tumor cells secrete chemokines to recruit more neutrophils, thereby further accelerating tumor progression.

Keywords: functional phenotype; immunosuppression; recurrent respiratory papillomatosis; tumor immune microenvironment; tumor-associated neutrophils.