Humanized Mouse Models for the Advancement of Innate Lymphoid Cell-Based Cancer Immunotherapies

Abstract

Innate lymphoid cells (ILCs) are a branch of the immune system that consists of diverse circulating and tissue-resident cells, which carry out functions including homeostasis and antitumor immunity. The development and behavior of human natural killer (NK) cells and other ILCs in the context of cancer is still incompletely understood. Since NK cells and Group 1 and 2 ILCs are known to be important for mediating antitumor immune responses, a clearer understanding of these processes is critical for improving cancer treatments and understanding tumor immunology as a whole. Unfortunately, there are some major differences in ILC differentiation and effector function pathways between humans and mice. To this end, mice bearing patient-derived xenografts or human cell line-derived tumors alongside human genes or human immune cells represent an excellent tool for studying these pathways in vivo. Recent advancements in humanized mice enable unparalleled insights into complex tumor-ILC interactions. In this review, we discuss ILC behavior in the context of cancer, the humanized mouse models that are most commonly employed in cancer research and their optimization for studying ILCs, current approaches to manipulating human ILCs for antitumor activity, and the relative utility of various mouse models for the development and assessment of these ILC-related immunotherapies.

Dissecting Tumor Growth: The Role of Cancer Stem Cells in Drug Resistance and Recurrence

“…For an in-depth understanding of CSCs and TME. ; and their interaction, an in vivo study was performed through xenograft models of highly immune-compromised NOD-SCID/IL2g-/- (NSG) mice, in which the growth capacity of CSCs was compromised-immune-cell-dependent, especially B-lymphocytes and natural killers (NKs) [ 147 , 148 ]. The published data show that the absence of immune cells may directly or indirectly influence tumor growth and the presence of cancer-initiating cells (CIC) [ 149 , 150 ].…”

“…For this reason, an experimental immunocompromised mice model is considered a robust method to understand the dependence of CSCs on TME. One of the most practical approaches to studying this relationship is the engraftment of a primary cell culture enriched in CSCs into immunocompromised mice [ 148 ]. The use of an adequate number of CSCs remains an important aspect, as is a matrix that supports precise implantation of cells in the exact inoculation site.…”

Mouse Models for Immune Checkpoint Blockade Therapeutic Research in Oral Cancer

“…Immune checkpoints are an area of interest to immuno-oncology, which seeks to modulate the immune system to identify and destroy cancerous cells [ 162 ]. Immune checkpoint blockers (ICBs) are a novel field in drug research and are developed to block ligand–receptor binding between T cells and cancer cells [ 163 ].…”

“…For example, the inhibitory receptors on NK cells that recognize MHC class I molecules differ and do not exhibit cross-reactivity (KIRs in humans and Ly49s in mice). Therefore, studying these receptors in immunocompetent mouse models is challenging; murine Ly49s do not bind to human MHC and vice versa [ 163 , 164 ]. Therefore, early research into NK/ILC checkpoint inhibitors depended on immunodeficient mice transplanted with human tumor cells and only one type of human immune cell.…”

Updates of Role of Stem Cells in Cancer Therapy

“…TME prompts the angiogenetic de novo development by means of CSC spread in the blood stream for metastatic dissemination. In vivo study was performed through xenograft models of highly immune compromised NOD-SCID/IL2g-/ -(NSG) mice, in which the growth capacity of CSCs was compromised-immune celldependent, particularly B-lymphocytes and natural killers (NKs) [142,143]. The published data show that the absence of immune cells may directly or indirectly impact tumour growth and the presence of cancer initiating cells (CIC) [144,145].…”