High B7‐H3 expression is linked to increased risk of prostate cancer progression

Abstract

B7-H3 is a member of the B7 superfamily of immune checkpoint molecules. B7-H3 up regulation has been linked to cancer development and progression in many tumors including prostate cancer. To clarify the potential utility of B7-H3 as a prognostic biomarker, B7-H3 expression was analyzed by immunohistochemistry in more than 17 000 prostate cancers. Normal prostatic glands were largely B7-H3 negative, while membranous B7-H3 immunostaining was seen in 47.0% of analyzed cancers. B7-H3 immunostaining was weak in 12.3%, moderate in 21.1% and strong in 13.5% of cases. High B7-H3 expression was associated with pT, Gleason score, lymph node metastasis, high Ki67 labeling index and early prostate-specific antigen recurrence (P < 0.0001 each). High B7-H3 expression was also linked to high androgen receptor expression and TMPRSS2:V-ets avian erythroblastosis virus E26 oncogene homolog (ERG) fusions (P < 0.0001 each). Multivariate analyses showed a strong independent prognostic impact of high B7-H3 expression in all cancers and in the ERG negative subgroup. Comparison with previously analyzed frequent chromosomal deletions revealed a close association with Phosphatase and Tensin Homolog deletions. Analysis of B7-H3, alone or in combination with other markers, might be of clinical utility, especially in the subgroup of ERG negative prostate cancers.

Association of B7‐H3 expression with racial ancestry, immune cell density, and androgen receptor activation in prostate cancer

“…B7 homolog 3 (B7‐H3) (PD‐L3, CD276) is a member of the B7 family of coregulatory molecules, 1 which also includes PD‐L1 (B7‐H1). In contrast to PD‐L1, B7‐H3 is widely expressed in prostate adenocarcinoma (PCa), and high expression has been associated with adverse pathologic features as well as a specific molecular phenotype 2‐6 . Accordingly, several previous studies have demonstrated an association between B7‐H3 expression and adverse oncologic outcomes in patients with surgically treated PCa, including early prostate‐specific antigen (PSA) recurrence 3‐5 as well as the development of castration‐resistant PCa (CRPC) and cancer‐specific death 4 .…”

“…Despite this progress, several unexplored areas remain as trials targeting B7‐H3 gain momentum. First, previous studies of B7‐H3 expression in PCa were conducted predominantly in European ancestry cohorts 2‐6 . Given recent evidence of differing immunobiology in prostate tumors arising in self‐identified Black (BL) patients compared with self‐identified White (WH) patients, 8‐12 we hypothesized that B7‐H3 expression may differ between races and could have a putative role in the differing immunobiology and immune therapy responses seen in these 2 groups of patients.…”

Pan-Cancer Analysis of Microfibrillar-Associated Protein 2 (MFAP2) Based on Bioinformatics and qPCR Verification

“…Among these, a type I transmembrane protein CD276 [ 30 ], recently identified as a promising target for tumor immunotherapy [ 31 ], is notable. Numerous studies have revealed that CD276 is overexpressed in a variety of tumors, including leukemia [ 32 ], breast cancer [ 33 ], prostate cancer [ 34 ], and other tumors, with expression levels strongly correlating with poor patient prognosis, and presumably involved in tumor immune evasion. In addition, CD276 has been shown to promote lactate production by promoting hexokinase 2 expression, thereby promoting glycolysis and drug resistance [ 35 ].…”

Immune Checkpoints, Inhibitors and Radionuclides in Prostate Cancer: Promising Combinatorial Therapy Approach

“…Like TIGIT, B7 homolog 3 (B7-H3), a member of the B7 family of the IgSF, is similar to PD-L1. B7-H3 is upregulated in PCa where it is negatively correlated with biochemical cancer recurrence, progression and metastasis [139]. Several studies have revealed increased B7-H3 expression that correlates with clinicopathologic indicators of aggressive cancer, metastasis and poor clinical outcomes in PCa patients [140][141][142][143].…”