Costimulatory molecule B7‐H1 in primary and metastatic clear cell renal cell carcinoma

Abstract

BACKGROUNDCancer 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.METHODSBetween 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.RESULTSVariable 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.CONCLUSIONSPatients 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. Cancer 2005. © 2005 American Cancer Society.

B7-H4 expression in renal cell carcinoma and tumor vasculature: Associations with cancer progression and survival

“…As in our prior B7-H1 studies (18,19), the association of tumor expression of B7-H4 with RCC progression and patient survival may have important implications for future therapy. Systemic IL-2 immunotherapy was the first Food and Drug Administration-approved treatment for metastatic RCC.…”

“…Specifically, we have demonstrated that aberrant RCC expression of the negative costimulatory ligand B7-H1 has been associated with increased disease progression and decreased cancer-specific survival (18,19). To date, however, studies pertaining to RCC tumor expression of B7-H4 have not been performed.…”

Identification and Characterization of MEDI4736, an Antagonistic Anti–PD-L1 Monoclonal Antibody

“…Indeed, the expression of PD-L1 is associated with reduced survival and an unfavorable prognosis in a number of cancers, including lung (10), renal (11)(12)(13), pancreatic (14)(15)(16), and ovarian (17). In contrast, the levels of tumor-infiltrating lymphocytes, and more specifically cytotoxic T cells, have been correlated with improved prognosis in a number of cancers (18).…”

Dynamic Immune Activation: Upregulation of Immune Inhibitory Pathways in Gastric Cancer

“…Additionally, to broaden the investigation for immune status of the same examined cohorts, it further revealed that patients with higher levels of other immune checkpoints, such as CTLA-4 and LAG-3, were significantly correlated with longer survival. However, the result seems paradoxical when compared to the previous studies with the opposite finding that higher levels of these immune inhibitory molecules are associated with worse outcomes [8][9][10][11]. One hypothesis was that up-regulation of these immunomodulatory molecules might reflect an immune activation status driven by effector immune cells as a feedback mechanism for the prevention of immune-associated adverse damage.…”