B7-H3 and its relevance in cancer immunological and non-immunological perspectives

Abstract

B7-H3 is a transmembrane glycoprotein and a member of the B7 family of proteins. It was previously known as an immunoregulatory molecule, shown in recent years to be of clinical significance in different types of cancer. In some tumor types high expression of B7-H3 has been linked to a poor prognosis, whereas in other cancers the opposite effect has been observed. Taken together, the precise role of B7-H3 in tumor immunity is unclear and further investigations are needed. Another aspect of B7-H3 that so far has received little interest is its role in non-immunological systems. We have demonstrated that knockdown of B7-H3 in melanoma and breast cancer cells results in both increased chemosensitivity and decreased metastatic potential. This has been observed in both in vitro and in vivo experiments. Several different signaling pathways seems to be involved, as B7-H3 knockdown can be linked to both higher expression of apoptotic markers and increased phosphorylation of Stat3. Increased knowledge of also the non-immunological role of B7-H3 protein is therefore of great biological and putative therapeutic interest.

Immune Surveillance Plays a Role in Locally Aggressive Giant Cell Lesions of Bone

“…This is similar to what has been shown in glioblastoma where B7-H3 expression by tumor cells was associated with greater local tumor invasiveness [31]. Similarly, a previous study showed silencing of B7-H3 reduced migration and invasion of melanoma and breast cancer cell lines [36]. B7-H3 has been associated with immune suppression and worse prognosis in multiple cancers including lung, glioblastoma, renal cell carcinoma, prostate, and pancreatic ductal adenocarcinoma cancer cells [11,15,31,44,58].…”

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

“…B7‐H3 exerts a pro‐oncogenic role in cancer cells, is implicated in tumor immunology (Nygren, Tekle, Ingebrigtsen, & Fodstad, ; Wang, Kang, & Shan, ), and has been proposed as target in many types of solid cancer (Picarda, Ohaegbulam, & Zang, ). In accordance with this, we found an antiproliferative effect on various melanoma cell lines by B7‐H3 knockdown by short hairpin RNAs as well as upon treatment with a monoclonal antibody targeting B7‐H3.…”

Breast Cancer Detection by B7-H3–Targeted Ultrasound Molecular Imaging

“…Recently, B7-H3 expression has been shown in several cancer types including acute leukemia, gastric, pancreatic, renal, liver, lung, bone, colon, prostate, ovarian, endometrial, and breast cancer (35–47). However, its role in immune response, including tumor immunity of different cancer types, remains unclear and controversial (33, 48, 49). Both T-cell co-stimulatory and inhibitory functions have been shown in various cancer types and B7-H3 expression has been correlated with both favorable and poor prognosis in cancer patients (33, 35, 50).…”