Immunoregulatory protein B7‐H3 promotes growth and decreases sensitivity to therapy in metastatic melanoma cells

Abstract

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B7-H3 in Cancer – Beyond Immune Regulation

“…B7-H3 also promotes resistance to cancer drugs. A growing number of studies show that inhibition or reduced expression of B7-H3 increases the response of tumor cells to drugs that target DNA replication, alkylating agents, and inhibitors of PI3K/Akt/mTOR and Ras/Raf/MEK signaling [4,6,9,10]. This further supports B7-H3 as a target in anticancer therapy, alone or in combination with other existing therapeutic modalities.…”

“…High-levels of soluble isoform are detected in the serum of cancer patients [3], which suggests soluble B7-H3 as a potential non-invasive biomarker. Finally, B7-H3 protein has also been found in the secretome, including exosomes and other extracellular vesicles [4]. B7-H3 is also expressed in tumor-associated endothelial cells, and high expression levels are associated with advanced tumor grade.…”

The type 1 transmembrane glycoprotein B7‐H3 interacts with the glycolytic enzyme ENO1 to promote malignancy and glycolysis in HeLa cells

“…B7-H3 is multifunctional but also noted for its dual role in immunoregulation and tumorigenesis compared to other immune checkpoints [13][14][15]. On the one hand, the role of B7-H3 in the tumor immunoregulation remains inconclusive; on the other, the function of B7-H3 and its downstream molecule in the proliferation and progression of tumor is incomplete.…”

B7-H3, a checkpoint molecule, as a target for cancer immunotherapy

“…Emerging studies have also demonstrated that B7-H3 may contribute to the resistance of anti-cancer drugs with various mechanisms. Proliferation and glycolytic capacity of metastatic melanoma cells were found to decrease when expression of B7-H3 was reduced or inhibited, leading to reduced resistance to chemotherapy as well as other targeted therapies [39]; this mechanism was further demonstrated to involve the inactivation of p38 MAPK signaling [40]. Similarly, glycolytic capacity was increased with the overexpression of B7-H3 in tumor cells, which induced the resistance to API-2 (triciribidine) and everolimus (RAD-001) [41].…”