Role of ILC2s in Solid Tumors: Facilitate or Inhibit?

Abstract

Group 2 innate lymphoid cells (ILC2s) are important mediators of type 2 immunity and play an important role in allergic diseases, helminth infections, and tissue fibrosis. However, the role of ILC2s in tumor immunity requires further elucidation. Studies over the past decade have reported that ILC2s play a promoting or suppressing role in different tumors. Here we reviewed the role of ILC2s in solid tumors demonstrating that ILC2s act as a crucial regulator in tumor immunity. We proposed that ILC2s could be an important predictor for tumor prognosis and a new therapeutic target after immunotherapy resistance. In conclusion, our study shed new light on modifying and targeting ILC2s for anti-tumor immunotherapy.

Type 2 innate lymphoid cells are not involved in mouse bladder tumor development

“…Nevertheless, it should be considered that all the factors involved in ILC2 pathways were not specifically targeted by the blocking antibodies used in our study, potentially leading to a partial neutralization of ILC2 activation and function. In addition to cytokine secretion and soluble factors, ILC2s can exert their functions through cell-to-cell contact (21), suggesting that direct interactions with other immune cells may contribute to the overall effects of ILC2s in the tumor microenvironment. To limit this bias in our investigations, we completed our study on ILC2s in bladder tumor development using transgenic ILC2-deficient mice.…”

“…Emerging evidence suggests that ILCs, including ILC2s, play significant roles in shaping the tumor microenvironment and antitumor immune response (18)(19)(20)(21). Tumor-infiltrating ILC2s have been reported to exert anti-tumor activity through direct interaction with T cells (22) or by inducing the recruitment of innate immune cells to the tumor such as eosinophils and dendritic cells, thereby improving T cell-mediated anti-tumor response in melanoma and pancreatic ductal adenocarcinoma (23, 24).…”

RAS signaling and immune cells: a sinister crosstalk in the tumor microenvironment

“…Even before tumor occurrence, KRAS inhibition reduced the number of Treg induced by tobacco carcinogen NNK in lung tissue [ 31 ]. Mechanically, KRAS signals further assist Tregs to promote GATA3/NOS2-related immunosuppression through the STING/ILC2 axis, thereby increasing lung metastatic load [ 32 , 33 ]. Similar results were seen in CRC and breast cancer.…”