CXCL12 is associated with FoxP3⁺ tumor-infiltrating lymphocytes and affects the survival of patients with oral squamous cell carcinoma

The role of tumor-infiltrating lymphocytes (TILs) suggests that cancer is a disease with not only a genetic, but also an immunological basis. Additionally, immune cell infiltration is an important feature of oral cancer. C-X-C motif chemokine ligand 12 (CXCL12) serves an important role in immune suppression in the tumor microenvironment. Therefore, the present study investigated how CXCL12 expression in oral squamous cell carcinoma (OSCC) was associated with clinicopathological parameters and TILs distribution. Complete CXCL12, TIL and clinical data were available for 45 patients with oral cancer treated by surgery. Expression levels of CXCL12, CD8⁺ TILs and forkhead box P3 (FoxP3⁺) TILs were assessed by immunohistochemistry in OSCC samples. CXCL12 expression in OSCC cells was observed in 32 (68.9%) cases and was associated with poor differentiation (P=0.045), advanced stages (P<0.001), tumor recurrence (P=0.011), poor overall survival (P=0.0476) and a higher density of FoxP3⁺ TILs (P<0.001). The CD8⁺/FoxP3⁺ ratio was lower in patients with poor differentiation (P=0.034), advanced stage tumors (P=0.015) and tumor recurrence (P=0.002). In addition, the ratio of CD8⁺/FoxP3⁺ TILs was significantly associated with the 5-year overall survival rate (P<0.001). The CD8⁺/FoxP3⁺ ratio was indicated to be a stronger prognostic indicator compared with the density of FoxP3⁺ TILs or CD8⁺ TILs. The present study identified an association between increased CXCL12 expression and FoxP3⁺ cell infiltration in OSCC. Targeting the CXCL12/C-X-C motif chemokine receptor 4 axis in OSCC may be employed as a novel strategy of tumor immunotherapy in the future.