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Published on: January 3, 2013
Costimulatory molecule B7-H1 in primary and metastatic clear cell renal cell carcinoma
R Houston Thompson1, Michael D Gillett, John C Cheville
1Department of Urology, Mayo Medical School, Mayo Clinic, Rochester, Minnesota 55905, USA.
Background:
Cancer cell expression of costimulatory molecule B7-H1 has been implicated as a potent inhibitor of T-cell-mediated antitumoral immunity. The authors recently reported that B7-H1 is aberrantly expressed in primary renal cell carcinoma (RCC). Blockade of B7-H1, as demonstrated in several murine cancer models, now represents a promising therapeutic target in RCC. However, the potential expression of B7-H1 in metastatic RCC has not been investigated. In the current study, the authors updated their primary RCC results with additional follow-up and investigated the potential role of B7-H1 in metastatic RCC.
Methods:
Between 2000 and 2004, 196 patients underwent nephrectomy and 26 patients had resection of RCC metastases for clear cell RCC. Immunohistochemical analysis was performed on tumor cryosections using a B7-H1 monoclonal antibody (clone 5H1). A urologic pathologist quantified the percentage of B7-H1-positive tumor cells and lymphocytes.
Results:
Variable levels of B7-H1 were expressed on primary RCC tumor cells (n = 130 [66.3%]) and primary tumor-infiltrating lymphocytes (n = 115 [58.7%]). Patients with high expression of B7-H1 on primary tumor cells and/or lymphocytes were significantly more likely to die of RCC compared with patients with low B7-H1 expression (risk ratio [RR] = 4.17; 95% confidence interval [95% CI], 1.97-8.84; P < 0.001) and this risk persisted in multivariate analysis after adjusting for the Mayo Clinic stage, size, grade, and necrosis score (RR = 2.63; 96% CI, 1.23-5.64; P = 0.013). Of the 26 metastatic specimens, cancer cell and lymphocyte B7-H1 expression were demonstrated in 17 (65.4%) and 18 (69.2%) specimens, respectively. In total, 14 (54.3%) metastatic specimens had high aggregate B7-H1 levels compared with 44.4% in primary RCC specimens.
Conclusions:
Patients with RCC with high B7-H1 expression were significantly more likely to die even after multivariate analysis. The authors also demonstrated that a high percentage of RCC metastases similarly harbored B7-H1. The authors surmised that B7-H1 blockade may augment current immunotherapy, including patients treated for metastases after cytoreductive nephrectomy.
Insights
High B7-H1 expression in renal cell carcinoma (RCC) correlates with increased mortality. This study found B7-H1 is also present in RCC metastases, suggesting B7-H1 blockade could enhance immunotherapy for advanced kidney cancer.
Area of Science:
- Immunology
- Oncology
- Medical Research
Background:
- B7-H1 (programmed death-ligand 1) is a molecule expressed by cancer cells that inhibits anti-tumor immune responses.
- Previous studies indicated aberrant B7-H1 expression in primary renal cell carcinoma (RCC).
- B7-H1 blockade is a potential therapeutic strategy for RCC, but its role in metastatic disease was unknown.
Purpose of the Study:
- To update findings on B7-H1 expression in primary RCC.
- To investigate B7-H1 expression in metastatic RCC.
- To assess the prognostic significance of B7-H1 in RCC.
Main Methods:
- Immunohistochemical analysis of B7-H1 expression on tumor cells and lymphocytes in 196 primary RCC and 26 metastatic RCC specimens.
- Quantification of B7-H1-positive cells by a urologic pathologist.
- Statistical analysis including risk ratio and multivariate analysis.
Main Results:
- High B7-H1 expression was observed in 66.3% of primary RCC tumor cells and 58.7% of tumor-infiltrating lymphocytes.
- Patients with high B7-H1 expression had a significantly higher risk of death from RCC (RR=4.17).
- B7-H1 was expressed in 65.4% of metastatic RCC cells and 69.2% of lymphocytes, with 54.3% showing high aggregate levels.
Conclusions:
- High B7-H1 expression is a significant negative prognostic factor in RCC, even after multivariate analysis.
- RCC metastases frequently express B7-H1, similar to primary tumors.
- Targeting B7-H1 may enhance immunotherapy for RCC, including patients with metastatic disease.
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