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Abstract
Simple SummaryGroup 2 innate lymphoid cells (ILC2s), like other ILCs, are a new resident cell subset of innate immunity that provides the first line of defense against pathogens such as helminths and largely contributes to inflammation observed in allergic disorders and in some tumors. They are considered sentinel cells, which reside at the interface between host and external environment and are rapidly activated by signals deriving from tissue. Depending on the type of signals and their high plasticity, ILC2s exert both enhancing and regulatory activity on other tissue-resident cells, including tumor- and tumor-associated cells. The functional profile of ILC2s, their pro- or antitumor activity in preclinical studies and patients and the potential therapeutic approaches targeting ILC2s have been extensively reviewed.Group 2 Innate Lymphoid Cells (ILC2s) belong to the family of helper ILCs which provide host defense against infectious agents, participate in inflammatory responses and mediate lymphoid organogenesis and tissue repair, mainly at the skin and mucosal level. Based on their transcriptional, phenotypic and functional profile, ILC2s mirror the features of the adaptive CD4+ Th2 cell subset, both contributing to the so-called type 2 immune response. Similar to other ILCs, ILC2s are rapidly activated by signals deriving from tissue and/or other tissue-resident immune cells. The biologic activity of ILCs needs to be tightly regulated in order to prevent them from contributing to severe inflammation and damage in several organs. Indeed, ILC2s display both enhancing and regulatory roles in several pathophysiological conditions, including tumors. In this review, we summarize the actual knowledge about ILC2s ability to induce or impair a protective immune response, their pro- or antitumor activity in murine models, human (children and adults) pathologies and the potential strategies to improve cancer immunotherapy by exploiting the features of ILC2s.
Highlights
Helper Innate Lymphoid cells (ILCs) are classified into four groups (ILC1s, ILC2s, ILC3s and lymphoid tissue-inducer—Lti—cells) mimicking the functional profiles of adaptive CD4+ Th cell subsets
In line with a protumor function of IL-33 in human colon–rectal carcinoma (CRC), the expression of the soluble form of IL-33R, was inversely associated with the malignant growth of CRC and metastasis [134]. Another possible target for the treatment of human acute promyelocytic leukemia (APL) is represented by the ILC2–myeloid-derived suppressor cells (MDSCs) axis, mostly driven by ILC2-produced IL-13: blocking any steps of this axis reversed the immunosuppression and significantly prolonged the survival time in humanized leukemic mice, while treating APL with retinoic acid reversed the increase in ILC2-induced MDSCs, as well as tumor- and ILC2-derived factors, in human patients with APL [32]
Even though the number of studies focusing on the role of ILC2s in controlling tumor growth has increased considerably in the last decade, at present, a clear definition of these cells in tumor microenvironments (TMEs) of different tumors is not available [155,156,157]
Summary
Helper Innate Lymphoid cells (ILCs) are classified into four groups (ILC1s, ILC2s, ILC3s and lymphoid tissue-inducer—Lti—cells) mimicking the functional profiles of adaptive CD4+ Th cell subsets. ILC2s are devoted to defending against pathogens, lymphoid organogenesis, tissue repair and type 2 inflammatory response in many immune-mediated disorders, including cancer [1]. Exploiting their multiple receptors, ILC2s can be rapidly activated by signals derived from tissue, playing a role as sentinel cells involved in the first line of defense against pathogens [2,3,4,5,6]. ILC2s exert both enhancing and homeostatic activities on several cells, including cancer cells and cells from tumor microenvironments (TMEs). We will summarize the main features of ILC2s, analyze their pro- or antitumor activity in different tumors and discuss the ILC2-targeted strategies to improve cancer immunotherapy
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