The potential of B7-H6 as a therapeutic target in cancer immunotherapy.

Abstract

Immune checkpoints are vital molecules that regulate T-cell function by activation or inhibition. Among the immune checkpoint molecules, the B7-family proteins are significantly involved in the immune escape of tumor cells. By binding to inhibitory receptors, they can suppress T-cell-mediated immunity. B7-family proteins are found at various stages of tumor microenvironment formation and promote tumorigenesis and tumor progression. B7-H6 (encoded by gene NCR3LG1) is a prominent member of the family. It has unique immunogenic properties and is involved in natural killer (NK) cell immunosurveillance by binding to the NKp30 receptor. High B7-H6 expression in certain tumor types and shortage of or low expression in healthy cells - except in cases of inflammatory or microbial stimulation - have made the protein an attractive target of research activities in recent years. The avoidance of NK-mediated B7-H6 detection is a mechanism through which tumor cells escape immune surveillance. The stimulation of tumorigenesis occurs by suppressing caspase cascade initiation and anti-apoptosis activity stimulation via the STAT3 pathway. The B7-H6-NKp30 complex on the tumor membrane activates the NK cells and releases both tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ). B7-H6 is highly expressed in a wide range of tumor cells, including glioma, hematologic malignant tumors, and breast cancer cells. Clinical examination of cancer patients indicated that the expression of B7-H6 is related to distant metastasis status and permits postoperative prognosis. Because of its unique properties, B7-H6 has a high potential be utilized as a biological marker for cancer diagnosis and prognosis, as well as a target for novel treatment options.

• Authors: Alaleh Mohammadi, Souzan Najafi, Mohammad Amini, Behzad Mansoori, Amir Baghbanzadeh, Jörg D Hoheisel, Behzad Baradaran
• Journal: Life sciences (Life Sci) Vol. 304 Pg. 120709 (Sep 01 2022) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 35697295 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2022. Published by Elsevier Inc.

Chemical References

• Natural Cytotoxicity Triggering Receptor 3

Topics

• Carcinogenesis
• Humans
• Immunotherapy
• Killer Cells, Natural
• Natural Cytotoxicity Triggering Receptor 3 (genetics, metabolism)
• Neoplasms (pathology)
• Tumor Microenvironment