Plastic Heterogeneity of Innate Lymphoid Cells in Cancer

ILCs are the most recently discovered lymphocytes that function in the innate immune system. These cells mediate immune and inflammatory responses, as well as regulate tissue homeostasis. ILCs have been implicated in dual tumor-suppressing and tumor-promoting activities. ILC plasticity is necessary for adaptation to a barrage of microenvironmental cues. Innate lymphoid cells (ILCs) fulfill important protective and reparative functions, and have thus been implicated in the maintenance of tissue homeostasis. Dysregulation of their activation is associated with several autoimmune and inflammatory diseases. The current literature on the role of ILCs in cancer is limited and our knowledge is therefore incomplete. Indeed, ILCs have been separately associated with tumor-promoting as well as tumor-suppressing activities, raising the need to understand the mechanisms by which these cells regulate tumor growth and progression toward a rational design of therapeutic approaches. We focus here on the heterogeneity of ILCs and discuss currently known mechanisms of their plasticity. Innate lymphoid cells (ILCs) fulfill important protective and reparative functions, and have thus been implicated in the maintenance of tissue homeostasis. Dysregulation of their activation is associated with several autoimmune and inflammatory diseases. The current literature on the role of ILCs in cancer is limited and our knowledge is therefore incomplete. Indeed, ILCs have been separately associated with tumor-promoting as well as tumor-suppressing activities, raising the need to understand the mechanisms by which these cells regulate tumor growth and progression toward a rational design of therapeutic approaches. We focus here on the heterogeneity of ILCs and discuss currently known mechanisms of their plasticity. cytotoxic effector cells that resemble cytotoxic T cells. cNK cells are able to recognize and destroy specific tumor and virus-infected cells in a major histocompatibility complex (MHC)- and antibody-independent manner. CD3+CD8+ effector T cells that release perforin and granzymes upon interaction with target cells that express cognate antigen, leading to the rapid apoptotic cell death of target cells. cells that act as sentinels in the immune system. DCs acquire and process antigens and present them to T cells in secondary or tertiary lymphoid organs to trigger antigen-specific immune responses. cells with granules that are stainable by the dye eosin. Eosinophils release cytotoxic cationic proteins and contribute to defense against parasites. They are also involved in asthma pathogenesis and allergy responses. cells that express factors required for the generation of secondary lymphoid organs during embryogenesis. LTi cells regulate the architecture of lymphoid tissue after birth. cells that can be further subdivided into classically (M1) and alternatively (M2) activated phenotypes. M1 macrophages secrete proinflammatory cytokines (e.g., TNF-α, IL-1β, IL-6), produce reactive oxygen and nitrogen species, and express high levels of MHCII molecules. M2 macrophages release anti-inflammatory cytokines (e.g., IL-10, TGF-β) and express high levels of scavenger, mannose, and galactose-type receptors. Whereas M2 macrophages are associated with type 2 responses, anti-inflammatory functions, tissue repair, remodeling, and angiogenesis, M1 macrophages serve as inducers of effector cells in type 1 responses and are tumoricidal. CD11b+Gr-1+ cells that possess strong immunosuppressive properties and interact with other immune cell types, including T cells, DCs, NK cells, and macrophages to regulate their functions. CD3+CD4+ T cells that inhibit effector B and T cells and express the transcription factor Foxp3. Tregs secrete anti-inflammatory cytokines (e.g., IL-10 and TGF-β), establish immune tolerance, and prevent autoimmune diseases. organs that include the spleen and lymph nodes as well as Peyer’s patches and mucosa-associated lymphoid tissues. Secondary lymphoid organs support lymphocyte homeostasis, maturation, and activation-induced differentiation. ectopic lymphoid formations found in chronically inflamed, infected, or tumoral tissues. TLSs display the structural characteristics of secondary lymphoid organs.