B7-H3 is a new cancer-specific endothelial marker in clear cell renal cell carcinoma

Abstract

BackgroundThe purpose of this study was to validate B7-H3 as a new cancer-specific endothelial marker in clear cell renal cell carcinoma.MethodsB7-H3 expression patterns were compared between cancer and paired adjacent normal renal parenchyma by immunohistochemistry in paraffin-embedded specimens from 200 consecutive patients with clear cell renal cell carcinoma from January to December 2010. Four corpus luteum specimens were used as physiologic angiogenesis controls. B7-H3 messenger (m)RNA levels representing circulating endothelial cells were analyzed in 24 peripheral blood samples using real-time polymerase chain reaction. Collection and processing of tissue and peripheral blood samples was performed in compliance with the Declaration of Helsinki.ResultsCancer cell-specific expression of B7-H3 was detected in 19% of clear cell renal cell carcinoma specimens, and tumor vasculature B7-H3 expression was confirmed in 98% (196) of cases. A diffuse pattern of vascular B7-H3 expression was associated with multiple adverse clinical and pathologic features (P<0.001). B7-H3 expression was not detected in paired adjacent normal renal parenchyma or vessels, or in luteal blood vessels. The B7-H3 mRNA level of circulating endothelial cells in peripheral blood was significantly higher in metastatic clear cell renal cell carcinoma (P<0.001).ConclusionThis pilot study indicates that B7-H3 is a cancer-specific endothelial marker of potential importance for the development of tumor-specific, vascular-targeted therapies, and is a prognostic marker in clear cell renal cell carcinoma.

New B7 Family Checkpoints in Human Cancers

“…Moreover, the presence of either tumor cell or diffuse tumor vasculature B7-H3 expression is significantly associated with an increased risk of death from RCC. This finding was confirmed by Guohai Shi’s group (30), indicating that B7-H3 is a cancer-specific endothelial marker of potential importance for the development of tumor-specific, vascular-targeted therapy, although the role of B7-H3 on tumor vasculature still remain unknown.…”

“…B7-H3 expression is significantly associated with poor outcome in patients with RCC (28–30), lung cancer (31), prostate cancer (32), CRC (33, 34), gallbladder cancer (35), esophageal squamous cancer (36), cervical cancer (37), osteosarcoma (OS) (38) and breast cancer (39). Thus, B7-H3 expression might be a feasible and effective means to predict the prognosis in cancer patients.…”

Eradication of Tumors through Simultaneous Ablation of CD276/B7-H3-Positive Tumor Cells and Tumor Vasculature

“…Because vessel co-option may contribute to resistance to current anti-angiogenic therapies (Bridgeman et al, 2016; Kuczynski et al, 2016), CD276 mAbs could aid in the effective targeting of both angiogenic and non-angiogenic tumor vasculature. In addition to tumor vessels, tumor cells also frequently overexpress CD276 (Brunner et al, 2012; Qin et al, 2013; Zang et al, 2010). We further validated CD276 expression on human tumors.…”

“…Thus, CD276 directed therapeutic mAbs may have a higher degree of specificity for tumor vessels than current anti-angiogenic agents that cannot distinguish physiological and pathological angiogenesis. Moreover, CD276 protein is also frequently overexpressed on tumor cells (Brunner et al, 2012; Qin et al, 2013; Zang et al, 2010). CD276 overexpression by tumor cells and Tumor ECs (TECs) makes it an appealing target for the development of therapeutic agents to simultaneously destroy both cell types.…”

New checkpoints in cancer immunotherapy

“…Recent studies found aberrant B7‐H3 expression on a wide variety of cancers, including stomach, lung, prostate, kidney, ovary, endometrium, colorectum, pancreas, liver, oral, bladder and breast …”