Panoply™ Human CDH5 Over-expressing Stable Cell Line

Cadherin 5 (CDH5) plays a crucial role in maintaining the adhesion and integrity of endothelial and vascular cells. CDH5 is aberrantly expressed in tumor cells and may have significant potential as a novel immune checkpoint. To better understand the role of CDH5 in tumors, researchers conducted a pan-cancer analysis. The results showed that CDH5 expression was downregulated in eight tumor types, including bladder cancer (BCa), and upregulated in four. In six tumor types, CDH5 was significantly associated with tumor stage and positively or negatively correlated with prognosis. Furthermore, CDH5 was strongly associated with tumor mutational burden (TMB) in 15 tumor types and microsatellite instability (MSI) in nine tumor types. KEGG-GSEA and Hallmarks-GSEA analyses showed that CDH5 was positively correlated with immune responses in most tumors. In many tumor types, CDH5 was positively correlated with immune cell infiltration. Enrichment analysis revealed that CDH5 was significantly associated with the expression of multiple immunomodulators and chemokines. Further experiments revealed that CDH5 expression is lower in BCa tissues and cell lines compared with adjacent normal tissues and normal urothelial cell lines, but is positively correlated with a better prognosis in BCa patients. In vitro co-culture experiments and ELISA assays demonstrated that CDH5 promotes the function of CD8+ T cells in the BCa tumor microenvironment. In summary, CDH5 is positively correlated with favorable tumor prognosis and effective immune responses, and holds promise as a new tumor marker and immune checkpoint.

qRT-PCR results showed that among seven bladder cancer cell lines, T24 cells expressed the lowest level of CDH5. Therefore, the researchers selected T24 cells to construct CDH5-overexpressing BCa cells. CDH5-overexpressing plasmids and corresponding control plasmids were successfully transfected into T24 cells (Figure 1A). CD8+ T cells were screened from the peripheral blood of healthy individuals. After activation with antibodies against CD3 and CD28, and IL-2, CD8+ T cells significantly expanded and grew in clusters (Figure 1B). Co-culture of CD8+ T cells with CDH5-overexpressing T24 cells enhanced their tumor cell-killing ability (Figure 1C). ELISA assays showed that CD8+ T cells co-cultured with CDH5-overexpressing T24 cells produced increased levels of IFN-γ and granzyme B (Figure 1D). In summary, CDH5 can promote the function of CD8+ T cells in the BCa TME.

Figure 1. CDH5 promoted the function of CD8⁺ T cells in BCa. (Li Y, et al., 2023)