Neutrophils play a dual role in the progression of head and neck cancer (HNC).  In tumor tissue, they exhibit anti- or pro-tumoral activity depending on factors of the microenvironment. Type I interferons (IFNs) have been shown to support the anti-tumoral phenotype of neutrophils, however, the mechanism underlying this phenotypic switch is not fully understood. We hypothesized that IFNAR-deficiency is critical at the early stages of granulopoiesis and may be responsible for the development of the pro-tumoral neutrophils.
Using bioinformatical approaches for arranging high-dimensional flow cytometry data we characterized and compared immune populations present in different organs of WT versus IFNAR-deficient mice. We demonstrated the presence of both mature neutrophils and progenitor cells within the tumor tissue of WT and IFNAR-deficient mice. We observed that the number of cells and size of population clusters, presumably consisting of progenitors, were significantly larger in Ifnar1-/- mice, compared to WT. We observed high expression of CD16/32 and Sca1 markers within subset of tumor-associated neutrophils that define populations of GMP and LSK cells respectively.
We suggest that type-I-IFN-signaling is crucial for the development of anti-tumoral neutrophils as it bias already the development and bone marrow retention of early myeloid progenitors. Tumor-driven emergency granulopoiesis causes the release of immature cells from bone marrow. Released cells accumulate within tumor tissue where they continue their maturation under the influence of tumor microenvironment. Knowing that tumors grow significantly faster in IFNAR1-deficient mice, we assume that disturbed type-I-IFNs-signaling change progenitor bias. As we observe a significant degradation of IFNAR also in our HNC patients, which positively correlate with poor prognosis, it is tempting to speculate that in human situation the same scenario occurs. Bearing this in mind, therapeutic approaches should be applied to skew the development of myeloid progenitors into antitumoral state to impair further tumor development and spread.