Resumen
In this manuscript, we demonstrated a particular chemokine axis (CXCR3/CXCL9,10,11) to be highly expressed in HPV-associated oropharynx carcinoma (HPVOPC). This classically paracrine chemokine axis is thought to play an anti-tumor role through immune surveillance and tumor suppression. More recently, however, the same axis has also been shown to have paradoxically a pro-tumor effect, whereby in an autocrine signaling fashion it increases tumor cell proliferation, angiogenesis, and metastasis in colorectal, breast, cervical, and gastric cancers, but this is the first time in HPVOPC. An athymic murine model demonstrates that CXCR3 antagonism does indeed inhibit tumor growth; however, CXCR3 antagonism in immunocompetent animals shows mixed results. The CXCR3 axis is implicated as a possible driver of malignancy in HPVOPC via tumor growth stimulation, though caution is warranted as inhibition of this axis may also adversely impact immunosurveillance. Further work is indicated to investigate opportunities for targeted therapy.