Neutrophil and Natural Killer Cell Interactions in Cancers: Dangerous Liaisons Instructing Immunosuppression and Angiogenesis

Abstract

The tumor immune microenvironment (TIME) has largely been reported to cooperate on tumor onset and progression, as a consequence of the phenotype/functional plasticity and adaptation capabilities of tumor-infiltrating and tumor-associated immune cells. Immune cells within the tumor micro (tissue-local) and macro (peripheral blood) environment closely interact by cell-to-cell contact and/or via soluble factors, also generating a tumor-permissive soil. These dangerous liaisons have been investigated for pillars of tumor immunology, such as tumor associated macrophages and T cell subsets. Here, we reviewed and discussed the contribution of selected innate immunity effector cells, namely neutrophils and natural killer cells, as “soloists” or by their “dangerous liaisons”, in favoring tumor progression by dissecting the cellular and molecular mechanisms involved.

The Good, the Bad, and the Ugly: Neutrophils, Angiogenesis, and Cancer

“…The effect of natural killer cells (NK cells) on angiogenic properties of neutrophils has been indicated [173]. By producing IFNγ and GM-CSF, NK cells have been shown to activate neutrophils and induce their surface expression of CD11b, CD62L, and CD64 [173].…”

“…After the activation by NK-derived factors, such neutrophils supported tumor angiogenesis by releasing VEGF and MMP-9. Moreover, they upregulated ARG1 expression, resulting in tumor growth [173], possibly by suppressing anti-tumoral T cell functions. On the other hand, Ogura et al demonstrated that NK-derived IFNγ is able to inhibit VEGF expression of neutrophil [174], once again showing the complexity of the cell-cell interactions in tumor angiogenesis.…”

Solubilized curcuminoid complex prevents extensive immunosuppression through immune restoration and antioxidant activity: Therapeutic potential against SARS-CoV-2 (COVID-19)

“…Neutrophils, which are important innate cells involved in the clearance of acute bacterial and viral infections, may help activate APCs, NK cells, and T cells [32] , [33] . To evaluate whether neutrophil activation is increased or decreased by C—S/M treatment, we next assessed neutrophil activation in CTX-injected mice following pre-treatment with C—S/M.…”

Transcriptomic Immune Profiles Can Represent the Tumor Immune Microenvironment Related to the Tumor Budding Histology in Uterine Cervical Cancer

“…FcγRIIIb/CD16b is mainly expressed by neutrophils and also negatively regulates neutrophil activities in the TIME [ 39 , 41 ]. Even though the interaction between neutrophils and NK cells in TIME is unclear, neutrophils can enhance NK-derived interferon (IFN)γ to suppress tumor progression and angiogenesis [ 42 , 43 , 44 ]. In addition, this study found that the FCGR3B expression level accurately predicts the TB status (AUC = 81.7%) and patient survival (high expression causes poor prognosis in OS, p = 0.0016).…”