Harnessing B7-H6 for Anticancer Immunotherapy: Expression, Pathways, and Therapeutic Strategies

Int J Mol Sci. 2024 Sep 25;25(19):10326. doi: 10.3390/ijms251910326.

Abstract

Cancer therapies have evolved from traditional chemotherapy to more precise molecular-targeted immunotherapies, which have been associated with improved side effects and outcomes. These modern strategies rely on cancer-specific biomarkers that differentiate malignant from normal cells. The B7 family of immune checkpoint molecules is crucial for cancer immune evasion and a prime therapeutic target. B7-H6, a recently identified member of the B7 family, has emerged as a promising therapeutic target. Unlike other B7 proteins, B7-H6 is not expressed in healthy tissues but is upregulated in several cancers. It binds to NKp30, activating natural killer (NK) cells and triggering immune responses against cancer cells. This review explores the expression of B7-H6 in different cancers, the factors that regulate its expression, and its intrinsic and extrinsic pathways. Additionally, we discuss potential anticancer therapies targeting B7-H6, highlighting its significance in advancing precision medicine. Understanding the role of B7-H6 in cancer immunity may inform the development of appropriate therapies that exploit its cancer-specific expression.

Keywords: B7-H6; NKp30; cancer-specific target; targeted therapy.

Publication types

  • Review

MeSH terms

  • Animals
  • B7 Antigens* / genetics
  • B7 Antigens* / metabolism
  • Biomarkers, Tumor / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunotherapy* / methods
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Natural Cytotoxicity Triggering Receptor 3 / genetics
  • Natural Cytotoxicity Triggering Receptor 3 / metabolism
  • Neoplasms* / genetics
  • Neoplasms* / immunology
  • Neoplasms* / metabolism
  • Neoplasms* / therapy
  • Signal Transduction

Substances

  • B7 Antigens
  • NCR3LG1 protein, human
  • Natural Cytotoxicity Triggering Receptor 3
  • NCR3 protein, human
  • Biomarkers, Tumor