Therapeutic manipulation of innate lymphoid cells

Abstract

Since their relatively recent discovery, innate lymphoid cells (ILCs) have been shown to be tissue-resident lymphocytes that are critical mediators of tissue homeostasis, regeneration, and pathogen response. However, ILC dysregulation contributes to a diverse spectrum of human diseases, spanning virtually every organ system. ILCs rapidly respond to environmental cues by altering their own phenotype and function as well as influencing the behavior of other local tissue-resident cells. With a growing understanding of ILC biology, investigators continue to elucidate mechanisms that expand our ability to phenotype, isolate, target, and expand ILCs ex vivo. With mounting preclinical data and clinical correlates, the role of ILCs in both disease pathogenesis and resolution is evident, justifying ILC manipulation for clinical benefit. This Review will highlight areas of ongoing translational research and critical questions for future study that will enable us to harness the full therapeutic potential of these captivating cells.

Cytomegalovirus Infection Impairs the Mobilization of Tissue-Resident Innate Lymphoid Cells into the Peripheral Blood Compartment in Response to Acute Exercise

“…This suggests that the pool of “sedentary” tissue-resident helper ILCs could be further maintained via regular exercise [ 33 ]. As such, acute exercise could be utilized as a possible future method to augment cell frequencies for transplantation, which can be isolated and expanded further from patients/donors and thus generate other ILC subsets in vitro more rapidly and economically than current approaches [ 34 ].…”

“…Emerging evidence suggests that ILCs play a crucial role in affecting clinical outcomes in diseased populations [ 34 , 35 ]. For example, acute leukemia patients with high frequencies of ILCs (especially ILC3) in the blood before chemotherapy and with allogeneic HSC transplantation displayed reduced risks of developing graft-versus-host disease (GVHD) compared to patients with a lower number of ILCs, indicating that ILCs have protective effects against potential tissue damage caused by GVHD, and regulating tissue integrity [ 35 ].…”

“…For example, acute leukemia patients with high frequencies of ILCs (especially ILC3) in the blood before chemotherapy and with allogeneic HSC transplantation displayed reduced risks of developing graft-versus-host disease (GVHD) compared to patients with a lower number of ILCs, indicating that ILCs have protective effects against potential tissue damage caused by GVHD, and regulating tissue integrity [ 35 ]. Helper ILCs constantly patrol the mucosal barrier surfaces, including those of the intestine, lungs, and spleen, and interact with other immune cells in the context of cancer; therefore, ILCs are considered potential target cells for anti-tumor benefits [ 34 ]. In addition, ILC2s are enriched in mucosal barriers and contribute to allergic asthma, mediated by type 2 inflammation, which negatively regulates ILC2 cells [ 36 ].…”

Therapeutic Potential of Innate Lymphoid Cells for Multiple Myeloma Therapy

“…Non-NK ILC’s relatively recent discovery with attendant ongoing challenges in characterisation [ 111 ], confounding predilection for plasticity [ 112 ], and their perception as being primarily non-cytotoxic action makes them less likely to appear in the first phase of ILC cell therapies [ 113 ]. Nonetheless, we explore some possible avenues for ILC cell therapy for MM.…”

Cord-Blood-Derived Professional Antigen-Presenting Cells: Functions and Applications in Current and Prospective Cell Therapies

“…Still, numerous pre-clinical trials are investigating the clinical feasibility and effectiveness of UCB-derived monocytes, MΦ, and DC ( Table 2 ). Though cellular therapies are starting to employ the prowess of B cells and ILCs in antitumor immunity [ 158 , 159 ], so far none have employed UCB to do so. The following section will provide insights into current and prospective cell therapies harnessing UCB-derived monocytes, MΦ, and DC in both mice and humans.…”