B7-H3 at the crossroads between tumor plasticity and colorectal cancer progression: a potential target for therapeutic intervention

Cancer Metastasis Rev. 2024 Mar;43(1):115-133. doi: 10.1007/s10555-023-10137-8. Epub 2023 Sep 28.

Abstract

B7-H3 (B7 homology 3 protein) is an important transmembrane immunoregulatory protein expressed in immune cells, antigen-presenting cells, and tumor cells. Studies reveal a multifaceted role of B7-H3 in tumor progression by modulating various cancer hallmarks involving angiogenesis, immune evasion, and tumor microenvironment, and it is also a promising candidate for cancer immunotherapy. In colorectal cancer (CRC), B7-H3 has been associated with various aspects of disease progression, such as evasion of tumor immune surveillance, tumor-node metastasis, and poor prognosis. Strategies to block or interfere with B7-H3 in its immunological and non-immunological functions are under investigation. In this study, we explore the role of B7-H3 in tumor plasticity, emphasizing tumor glucose metabolism, angiogenesis, epithelial-mesenchymal transition, cancer stem cells, apoptosis, and changing immune signatures in the tumor immune landscape. We discuss how B7-H3-induced tumor plasticity contributes to immune evasion, metastasis, and therapy resistance. Furthermore, we delve into the most recent advancements in targeting B7-H3-based tumor immunotherapy as a potential approach to CRC treatment.

Keywords: B7-H3; Colorectal cancer; Drug resistance; Immunomodulation; Tumor plasticity, immune checkpoint.

Publication types

  • Review

MeSH terms

  • B7 Antigens* / metabolism
  • Colorectal Neoplasms* / pathology
  • Humans
  • Immunotherapy
  • Tumor Microenvironment

Substances

  • B7 Antigens
  • CD276 protein, human