The CXCL11-CXCR3A axis influences the infiltration of CD274 and IDO1 in oral squamous cell carcinoma.

Background: The CXCL9/10/11-CXCR3 axis plays pivotal roles in the recruitment of immune cells and the formation of cancer-specific immunity in various cancers. High expression of immune checkpoints, which could be regulated by cytokines, is closely related to the establishment of immune escape in tumor microenvironment. Therefore, the study was tried to provide insights into the influence of the CXCL9/10/11-CXCR3 axis on immune checkpoints in oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs), especially oral leukoplakia (OLK).

Methods: The mRNA levels of CXCL9/10/11 and CXCR3 were analyzed in TCGA, GEO and Oncomine and verified in OLK and OSCC. The specimens were used to analysis the relationship between CXCL9/10/11 and CXCR3 variants. The correlation between CXCL9/10/11 and immune checkpoint/ligand in head and neck squamous cell carcinoma was analyzed in TIMER and confirmed in samples. Small interference transfection of CXCL11 in SCC25 cells was used to evaluate the function of CXCL11 on CD274/IDO1 expression.

Results: CXCL9/10/11 had increase expression trends from normal tissues to OSCC. The proportion of CXCR3A (one variant of CXCR3) was significantly increased in OSCC comparing with normal tissues, while other variants-CXCR3B and CXCR3alt-did not. CXCL9/10/11 was positively correlated with CXCR3A and immune checkpoints/ligand (IDO1, LAG3, and CD274) in OLK and OSCC. CXCL11-knockdown SCC25 cells could directly inhibit the intracellular expression of CD274 and IDO1.

Conclusion: The upregulated CXCL9/10/11-CXCR3A axis may interact with immune checkpoints/their ligands in OLK and OSCC. Furthermore, CXCL11 may affect the expression of CD274 and IDO1 in an autocrine mode in OSCC.