Introduction

Neutrophils play a crucial role in the tumor microenvironment (TME) of head and neck squamous cell carcinomas (HNSCC) and significantly influence treatment outcomes. Phenotypic and functional properties of neutrophils adapt to the TME with distinct subsets modulating disease progression and therapeutic interventions.

Material and Methods

Peripheral neutrophils from HNSCC patients and healthy donors were purified and their capacity to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) tested using an impedance-based assay and an engineered EGFR-directed IgA2 antibody vs. Panitumumab as clinical benchmark. Multicolor immunofluorescence and flow cytometry was performed to detect phenotypical switches and involved subsets of HNSCC-patient-derived neutrophils compared to control.

Results

We observed significant phenotypic differences between neutrophils from healthy donors and HNSCC patients. Gender and tumor stage influenced neutrophil phenotypes and their ability to lyse tumor cells through ADCC. Patients with advanced HNSCC and males may benefit less from neutrophil-centered immunotherapy. The engineered IgA2 antibody demonstrated superior efficacy in activating neutrophils for ADCC compared to Panitumumab using healthy and patient-derived neutrophils.

Discussion

There seems to be a remarkable potency of the IgA isotype as a therapeutic alternative for tumor immunotherapy. The distinct behavior and antibody-isotype dependent ADCC competence of CD177+/- neutrophils of healthy donors warrants further exploration. Our study emphasizes the importance of personalized immunotherapy treatments considering the characteristics of neutrophils, patients, and the type of antibody to improve ADCC and enhance treatment outcomes for HNSCC.

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