Panoply™ Human CD74 Over-expressing Stable Cell Line

Chronic obstructive pulmonary disease (COPD) affects the incidence and prognosis of lung cancer. COPD patients have a significantly increased risk of developing lung squamous cell carcinoma (LSCC). COPD may promote an immunosuppressive microenvironment in LSCC by regulating the expression of immunosuppressive factors in T cells, but the mechanism is unclear. Here, researchers showed that LSCC in COPD patients had an increased proportion of tumor-associated macrophages (TAMs) and elevated levels of CD8+ T cell exhaustion molecules, which led to the formation of an immunosuppressive microenvironment. Further analysis revealed the presence of a critical CD74+ tumor cell population that expressed both epithelial and immune cell features, had a stronger tumorigenic capacity, and predicted worse overall survival. Notably, migration inhibitory factor (MIF) secreted by tumor-associated lymphocytes (TAMs) in laryngeal squamous cell carcinoma (LSCC) with chronic obstructive pulmonary disease (COPD) may promote CD74 activation. MIF-CD74 may interact with CD8+ T cells and impair their antitumor activity by regulating the PI3K-STAT3-programmed cell death-1 ligand 1 signaling pathway, thereby promoting tumor proliferation and immune escape.

To further investigate the function of CD74, the researchers used KLN205 (mouse lung squamous cell carcinoma line) cells to construct CD74 overexpression (CD74-Over) cells and CD74 knockdown (CD74-KD) cells. They observed that CD74-Over cells did not show significant LC proliferation in vitro. Tumor growth assays were performed after inoculation of CD74-NC, CD74-Over, and CD74-KD KLN205 cells in C57BL/6 mice. In C57BL/6 mice, the tumorigenic ability of CD74-KD KLN205 cells was significantly reduced, as shown in Figure 1A-C. In addition, treatment with the MIF inhibitor 4-IPP also significantly inhibited tumor growth. However, this effect of CD74-KD KLN205 cells was not significant in immunodeficient mice (Figure 1D-F). These results suggest that CD74 may promote tumor cell proliferation by interacting with immune cells.

Figure 1. The tumorigenic potential of CD74+ tumour cells. (Wang D, et al., 2024)