Innate Lymphoid Cells: Role in Immune Regulation and Cancer

Simple Summary Innate lymphoid cells (ILCs) are an emerging family of effector cells known to play a major role in innate defenses against pathogens, lymphoid organogenesis, tissue repair, and homeostasis. They are positioned strategically within tissues to provide the first line of defence and shape the ensuing adaptive immune cell response. Recent evidence suggests that ILCs contribute to immune regulation in different diseases, including cancer, and can have significant impact on disease outcome. In this review, we highlight the immunosuppressive roles of ILCs in cancer that inhibit effective immune surveillance and anti-tumour response. Immune regulation is composed of a complex network of cellular and molecular pathways that regulate the immune system and prevent tissue damage. It is increasingly clear that innate lymphoid cells (ILCs) are also armed with immunosuppressive capacities similar to well-known immune regulatory cells (i.e., regulatory T cells). In cancer, immunoregulatory ILCs have been shown to inhibit anti-tumour immune response through various mechanisms including: (a) direct suppression of anti-tumour T cells or NK cells, (b) inhibiting T-cell priming, and (c) promoting other immunoregulatory cells. To provide a framework of understanding the role of immunosuppressive ILCs in the context of cancer, we first outline a brief history and challenges related to defining immunosuppressive ILCs. Furthermore, we focus on the mechanisms of ILCs in suppressing anti-tumour immunity and consequentially promoting tumour progression.