Neutrophil-T-cell interactions in tumor-draining lymph nodes in a head and neck cancer model

Neutrophils have been shown to exhibit protumor or antitumor properties in the tumor microenvironment depending on cytokine stimulation. Stimulation by the cytokine Interferon (IFN) leads to the exhibition of antitumor effects which are achieved via stimulation of T-cells by neutrophils. Unlike the immediate tumor microenvironment, tumor-draining lymph nodes (LN) have not been investigated regarding neutrophil activity. Tumor-draining LN are the first organs of metastasis in head and neck cancer and have high prognostic and therapeutic relevance. In this study, we investigated whether neutrophils exhibit protumor or antitumor properties in tumor-draining LN.

Tumor-associated LN were imaged via two-photon microscopy in a murine head and neck cancer model. Neutrophils and T-cells were fluorescently labeled to allow for in vivo analysis of cell interactions. In order to assess IFN-associated antitumoral properties of neutrophils, IFN-receptor-deficient mice (pro-tumoral environment) were compared to wild-type mice. We compared mice with and without tumors in both groups.

Tumor-draining LN had more neutrophils than LN in tumor-free mice. Tumor-bearing, IFN-receptor-deficient mice had higher neutrophil counts in tumor-draining LN than wild type mice, however, neutrophil-T-cell interactions were significantly reduced in IFN-deficient mice compared to wildtype mice.

The results of this study suggest an increased immunologic activity in tumor-draining LN. IFN-mediated promotion of neutrophil-T-cell interaction suggests anti-tumoral neutrophil activity in tumor-draining LN and potentially enables novel therapeutic approaches.

Publikationsverlauf

Publikationsdatum:
23. April 2019 (online)