Potential Therapeutic Targets of B7 Family in Colorectal Cancer

Abstract

Programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway blockade has impressively benefited cancer patients with a wide spectrum of tumors. However, its efficacy in colorectal cancer (CRC) is modest, and only a small subset of patients benefits from approved checkpoint inhibitors. Newer checkpoints that target additional immunomodulatory pathways are becoming necessary to activate durable antitumor immune responses in patients with CRC. In this review, we evaluated the mRNA expression of all 10 reported B7 family members in human CRC by retrieving and analyzing the TCGA database and reviewed the current understanding of the top three B7 family checkpoint molecules (B7-H3, VISTA, and HHLA2) with the highest mRNA expression, introducing them as putative therapeutic targets in CRC.

Keywords: B7-H3; HHLA2; VISTA; colorectal cancer; immune checkpoint.

FIGURE 1

Heatmap analysis of the mRNA expression of B7 family members in CRC tumors shown as scaled log₂-fold changes (GEPIA using data from TCGA).

FIGURE 2

The regulatory mechanisms of B7-H3, VISTA, and HHLA2 in tumor microenvironments. B7-H3, VISTA, and HHLA2 are potential immune checkpoint molecules that interact with their receptors resulting in antitumor immune responses within tumor microenvironments.