Innate lymphoid cells (ILCs) have potent immune functions in experimental conditions in mice, but their contribution to immunity in natural conditions in humans remains unclear. We investigated the presence of ILCs in a cohort of patients with severe combined immunodeficiency (SCID). All ILC subsets were absent in SCID patients carrying mutations of IL2RG or JAK3. T cell reconstitution was observed in SCID patients upon hematopoietic stem cell transplantation (HSCT), but the patients still exhibited drastic reduction of ILCs in the absence of myeloablation, at the exception of rare cases of ILC1 reconstitution. Remarkably, the observed ILC deficiencies were not associated with any particular susceptibility to disease, with a follow-up extending from 7 to 39 years after HSCT. We thus report here the first cases of selective ILC deficiency in humans, and show that ILCs may be dispensable in natural conditions, if T cells are present and B cell function is preserved.
The world of lymphocytes has recently expanded. A group of cells, innate lymphoid cells (ILC), has been defined. It includes lymphoid cells that have been known for decades, such as natural killer (NK) cells and lymphoid tissue-inducer (LTi) cells. NK cells recognize a vast array of tumor cells, which they help to eliminate through cytotoxicity and the production of cytokines, such as IFNg. Advances in our understanding of NK-cell biology have led to a growing interest in the clinical manipulation of these cells in cancer. The other ILCs are found mostly in the mucosae and mucosal-associated lymphoid tissues, where they rapidly initiate immune responses to pathogens without the need for specific sensitization. Here, we outline the basic features of ILCs and review the role of ILCs other than NK cells in cancer. Much of the role of these ILCs in cancer remains unknown, but several findings should lead to further efforts to dissect the contribution of different ILC subsets to the promotion, maintenance, or elimination of tumors at various anatomic sites. This will require the development of standardized reagents and protocols for monitoring the presence and function of ILCs in human blood and tissue samples.
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