The relevance of B7-H3 and tumor-associated macrophages in the tumor immune microenvironment of solid tumors: recent advances.

Abstract

B7 homolog 3 (B7-H3) is a member of the B7 ligand family. It is highly expressed in various human cancers, especially mesenchymal malignancies. B7-H3 regulates cancer progression through multiple signaling pathways such as JAK2/STAT3, NF-κB, PI3K/AKT, and ERK. It also has the ability to downregulate CD8⁺ T-cell infiltration and drive immune evasion. Tumor-associated macrophages (TAMs) are the primary immune infiltrating cells in diverse solid tumors, dominating the immune environment of these malignancies. B7-H3 may have connections to TAMs through the induction of polarization and immunosuppression by the CCL2-CCR2-M2 macrophage axis. This mechanism can inhibit antitumor immunotherapy and promote tumor progression in non-small cell lung cancer, ovarian cancer, colorectal cancer, and osteosarcoma. The inducibility of B7-H3 in TAMs provides novel insight into the targeting of checkpoints for tumor immunotherapy. In general, B7-H3 represents a promising immune therapeutic target and should be considered an immunologic adjuvant for activating the tumor immune microenvironment. Therefore, combination therapies based on anti-B7-H3 agents hold great potential for improving the solid tumor microenvironment to enhance the initiation of the cancer-immunity cycle.