Tumor cells inhibit the activation of ILC2s through up-regulating PD-1 expression

Abstract

Objective

Up-regulating programmed cell death ligand-1(PD-L1) expressed on tumor cells and tumor-infiltrating myeloid cells interacting with up-regulated programmed cell death-1 (PD-1) expressed on tumor-infiltrating lymphoid cells greatly hinder their tumor-inhibiting effect. It is necessary to explore the deep mechanism of this negative effect, so as to find the potential methods to improve the immunotherapy efficiency.

Methods and Results

In this study, we found that the PD-1 expression in lung cancer-infiltrating type II innate lymphoid cells (ILC2s) was highly up-regulated, which greatly restrained the activation and function of ILC2s. Furthermore, anti-PD-1 could restore the inhibition and effective cytokine secretion of ILC2s when co-cultured with tumor cells. In vivo studies proved that anti-PD-1 treatment promoted the activation of tumor-infiltrating ILC2s and inhibited the tumor growth of LLC-bearing nude mice.

Discussion

Our studies demonstrate a new PD-1/PD-L1 axis regulating mechanism on innate immune cells, which provide a useful direction to ILC2s-based immunotherapy to cancer diseases.

Keywords:

• Lung cancer
• PD-l1
• PD-1
• ILC2s
• cancer microenvironment

Ethical approval

All authors provided consent for publication. We declare that all methods are reported in accordance with the Guide for Care and Use of Laboratory Animals.

Author contributions

Chaoyun Yin did the research and wrote the manuscript. Yani Pan, Guangyu Li and Qiang Chen modified the language. Xizu Wang and Xijun He revised the study. Huangao Zhou designed the study, drafted, and revised the manuscript. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The conclusion figures have been uploaded and the tables supporting the view of this review have been listed in the article.

Additional information

Funding

This work was supported by the "Jiangyin City Science and Technology Innovation Special Fund" [grant no. JY0603A011014220062PB].