Abstract
Innate lymphoid cells (ILCs) were found to be developmentally related to natural killer (NK) cells. In humans, they are mostly located in “barrier” tissues where they contribute to innate defenses against different pathogens. ILCs are heterogeneous and characterized by a high degree of plasticity. ILC1s are Tbet+, produce interferon gamma and tumor necrosis factor alpha, but, unlike NK cells, are non-cytolytic and are Eomes independent. ILC2 (GATA-3+) secrete type-2 cytokines, while ILC3s secrete interleukin-22 and interleukin-17. The cytokine signatures of ILC subsets mirror those of corresponding helper T-cell subsets. The ILC role in defenses against pathogens is well-documented, while their involvement in tumor defenses is still controversial. Different ILCs have been detected in tumors. In general, the conflicting data reported in different tumors on the role of ILC may reflect the heterogeneity and/or differences in tumor microenvironment. The remarkable plasticity of ILCs suggests new therapeutic approaches to induce differentiation/switch toward ILC subsets more favorable in tumor control.
Highlights
Innate lymphoid cells (ILCs) belong to a family of immune cells involved in innate host defenses against pathogens and tumors
While natural killer (NK) cell activation and function is under the control of inhibitory receptors such as the HLA-I-specific KIR and CD94/NKG2A and PD-1, limited information exists on checkpoints possibly expressed by ILC3
While the first seminal evidences of the consequence of cell polarization at the tumor site were provided by Mantovani and colleagues for tumor-associated macrophages [55], other innate cell types present in the tumor microenvironment (TM) were subsequently shown to favor tumor escape from antitumor immune responses
Summary
Innate lymphoid cells (ILCs) belong to a family of immune cells involved in innate host defenses against pathogens and tumors. Kim et al reported that growth of lymphoma cells injected subcutaneously in mice could be inhibited by local overexpression of IL-33, a major cytokine promoting differentiation and function of ILC2s In this model, it was shown that ILC2s mediate antitumor activity either by producing cytokines relevant in tumor control (IL-5, IL-13, and GMCSF) or by producing CXCR2 ligands (CXCL1 and CXCL2), which could induce the apoptosis of CXCR2+ tumor cells [34]. Since IL-23 plays an important role in ILC3 development, it is not surprising that, as suggested by some studies [34, 35], the ILC3-derived IL-17 and IL-22 may contribute to the development of colorectal cancers In this context, transgenic overexpression of IL-23 in wild-type mice was shown to be sufficient to induce adenoma formation in an ILC3-dependent manner, partly through IL-17 production [37]. Conflicting available data could reflect, at least in part, the heterogeneity of ILC3 subsets, the tissue of origin, and the type of microenvironment of different tumors
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