Luciferase Reporter Cell Line - RM-1

Activation of Yes-associated protein 1 (YAP1) is a common feature of prostate cancer (PCa). Here, researchers found that YAP1 is typically highly expressed in PCa tissues. Transcriptomic analysis showed that PD-L1 and the immune co-stimulatory molecule CD70 were persistently upregulated in YAP1-activated PCa cells. Simultaneously, CD70 was also highly expressed in patients unresponsive to immune checkpoint blockade therapy (ICB), but absent in ICB-responsive patients, who typically exhibit higher cytotoxic T-cell infiltration. More importantly, inhibition of CD70 restored the sensitivity of YAP1-activated PCa cells to PD-1 inhibitors. Mechanistically, YAP1 directly regulates CD70 transcription through synergy with the DNA-binding factor RUNX1. Therefore, upregulation of CD70 inhibits immune cell infiltration into malignant lesions and promotes CD8+ T-cell exhaustion, thereby helping tumors evade immune surveillance. In summary, these results indicate that the YAP1-CD70 signaling pathway represents a novel immunosuppressive mechanism in prostate cancer (PCa).

Here, researchers hypothesized that CD70 might be a potential factor mediating resistance to immune checkpoint blockade (ICB) therapy in prostate cancer (PCa) patients. They evaluated the antitumor efficacy of anti-PD-1 and anti-CD70 antibodies using two independent PCa orthotopic allogeneic transplantation mouse models. C57BL/6 mice were orthotopically injected with RM-1-Luc and then treated with either an IgG isotype control or a monoclonal antibody. Images were taken every 5 days starting one week after cell injection until the end of treatment. As expected, combined blockade significantly inhibited the growth of allogeneic tumors and promoted the function of CD8+ T cells (Figure 1K-M). Importantly, CD70 expression exhibited strict temporal regulation, rapidly downregulating upon antigen withdrawal.

Figure 1. Representative bioluminescence images, growth and survival curve of C57BL/6 mice that were orthotopically injected with RM-1-Luc and treated with IgG isotype control or monoclonal antibody. (Tong T, et al., 2026)