Abstract
Innate lymphoid cells (ILCs) represent the most recently identified subset of effector lymphocytes, with key roles in the orchestration of early immune responses. Despite their established involvement in the pathogenesis of many inflammatory disorders, the role of ILCs in cancer remains poorly defined. Here we assessed whether human ILCs can actively interact with the endothelium to promote tumor growth control, favoring immune cell adhesion. We show that, among all ILC subsets, ILCPs elicited the strongest upregulation of adhesion molecules in endothelial cells (ECs) in vitro, mainly in a contact-dependent manner through the tumor necrosis factor receptor- and RANK-dependent engagement of the NF-κB pathway. Moreover, the ILCP-mediated activation of the ECs resulted to be functional by fostering the adhesion of other innate and adaptive immune cells. Interestingly, pre-exposure of ILCPs to human tumor cell lines strongly impaired this capacity. Hence, the ILCP-EC interaction might represent an attractive target to regulate the immune cell trafficking to tumor sites and, therefore, the establishment of an anti-tumor immune response.
Highlights
Innate lymphoid cells (ILCs) constitute the latest described family of innate lymphocytes with key functions in the preservation of epithelial integrity and tissue immunity throughout the body (Mjösberg and Spits, 2016)
We report that the innate lymphoid cell precursors (ILCPs)-mediated activation of the endothelial cells (ECs) is functional, i.e., it allows the adhesion of freshly isolated peripheral blood (PB) immune cells
In particular we identify ILCPs as the only competent circulating ILC subset in inducing EC activation through the upregulation of adhesion molecules on the EC surface
Summary
Innate lymphoid cells (ILCs) constitute the latest described family of innate lymphocytes with key functions in the preservation of epithelial integrity and tissue immunity throughout the body (Mjösberg and Spits, 2016). The different ILC subsets have important effector functions during the early stages of the immune response against microbes, in tissue repair and in the anatomical containment of commensals at surface barriers (Hazenberg and Spits, 2014). Scant data are available about the interaction between human ILCs and the vascular endothelium, which constitutes the physical barrier to be crossed by peripheral blood (PB) immune cells to migrate into tissues where to exert their effector functions (Nourshargh et al, 2010). We show for the first time that human primed ILCPs can interact with endothelial cells (ECs), upregulate adhesion molecules, and stimulate their pro-inflammatory cytokine secretion. This activation occurs through NF-kB, primarily in a contact-dependent manner that engages surface. We have unraveled a cell intrinsic ability of ILCPs that might be selectively impaired by tumors to favor their immune escape
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