Panoply™ Human CD248 Over-expressing Stable Cell Line

Tumor immune evasion is a key step in tumor progression. Cancer-associated fibroblasts (CAFs) within the tumor microenvironment (TME) express abundant PD-L1 and suppress CD8+ T cell function, thereby enabling immune evasion. CD248 is a candidate biomarker for non-small cell lung cancer (NSCLC)-associated CAFs, although its role in immune evasion remains unclear. Here, researchers demonstrate that CD248 increases PD-L1 levels in CAFs, inhibits CD8+ T cell function, and promotes NSCLC cell invasion and migration. CD248-induced activation of the FAK/Src/JNK/c-Jun axis promotes PD-L1 expression on CAFs. In tumor-bearing mice, lung cancer growth is significantly slowed, and fibroblast-specific CD248 knockout mice have higher numbers of granzyme B+ CD8+ T cells than wild-type mice. Importantly, the efficacy of tislelizumab is enhanced in CD248 knockout mice. These findings suggest that CD248 activates FAK/Src/JNK/c-Jun, thereby inducing PD-L1 expression on CAFs, thereby promoting immune escape of NSCLC.

To evaluate whether non-small cell lung cancer (NSCLC)-derived CAFs express PD-L1, researchers performed IF staining to detect CD248 and PD-L1 in NSCLC tissues and NATs. Results showed elevated PD-L1 expression in NSCLC samples, with significant colocalization of CD248 and α-SMA (Figure 1A). qPCR analysis revealed significantly higher PD-L1 mRNA levels in CAFs than in NFs (Figure 1B). These results were further validated by Western blotting, which showed increased PD-L1 protein expression in CAFs compared with NFs (Figure 1C). To explore the relationship between CD248 and PD-L1 expression in CAFs, qPCR was performed on CD248-overexpressing CAFs (CAFs-CD248OE), CD248-knockdown CAFs (CAFs-sh-CD248), and control CAFs (CAFs-sh-CON). Compared with the control group, PD-L1 expression was significantly decreased in CD248-knockdown CAFs, whereas expression was increased in CD248-overexpressing CAFs (Figure 1D). Western blot analysis further confirmed that CD248 knockdown reduced PD-L1 protein levels. Concomitantly, CD248 overexpression led to increased PD-L1 expression in CAFs (Figure 1E). IF staining consistently demonstrated a stronger PD-L1 signal in tissues containing CD248-overexpressing CAFs (Figure 1F). These results indicate that CD248+ CAFs upregulate PD-L1 expression.

Figure 1. CD248+CAFs express high levels of PD-L1. (Yang Z, et al., 2025)