Panoply™ Human TNFRSF18 Over-expressing Stable Cell Line

Colorectal cancer (CRC) is one of the most common digestive system malignancies worldwide and is associated with poor survival outcomes. CD8⁺ T cell exhaustion plays a crucial role in promoting tumor immune evasion. However, the dynamic evolution of CD8⁺ T cell exhaustion in CRC patients with different TNM (tumor-node-metastasis) stages and its impact on clinical prognosis remain incompletely elucidated. Here, researchers revealed how TNM stage in CRC patients influences CD8⁺ T cell exhaustion through differential TNFRSF18/CXCL13 dynamics and ribosomal stemness. TNFRSF18 expression is significantly higher in T cells infiltrating tumor tissue than in adjacent non-tumor areas, and CD8⁺ T cells with high TNFRSF18 expression exhibit distinct exhaustion characteristics. During colorectal cancer progression, TNM-stage-driven remodelling of the tumour microenvironment (TME) induced progressive CD8⁺ T cell exhaustion marked by declining TNFRSF18 and rising CXCL13 expression in tumour-infiltrating T cells elevation of both markers in the tumour compared with adjacent tissues. Furthermore, the researchers found that tumor cells exhibited elevated expression of stem cell-associated ribosomal genes (RPS7, RPL8, RPL30), peaking at T4 stage and associated with poor prognosis and immune evasion.

In CD4⁺ T cells, TNFRSF18-positive expression promoted TNF binding to TNFR2 and activated the atypical NF-κB pathway (Figure 1D), while CXCL13-positive expression enhances PD-1 signaling. Both TNFRSF18 and CXCL13 are key regulators of T cell function and influence the TNF signaling pathway. The researchers then generated a TNFRSF18-overexpressing Jurkat T cell line and performed RT-qPCR to assess the effect of TNFRSF18 overexpression on T cell activation in Jurkat cells. As shown in Figures 1E and 1F, TNFRSF18-overexpressing Jurkat cells significantly reduced TNF-α and IFN-γ mRNA levels, indicating that TNFRSF18 inhibits T cell effector cytokine production, supporting its role in promoting T cell exhaustion.

Figure 1. The immune regulatory role of TNFRSF18 in T cells was investigated through overexpression experiments. (Jia T, et al., 2025)