CXCR6 expression as a predictive biomarker for immunotherapy responsiveness in nasopharyngeal carcinoma

Abstract

Immunotherapy breakthroughs have revolutionized the treatment of nasopharyngeal carcinoma (NPC). The addition of toripalimab to gemcitabine-cisplatin (GP) chemotherapy as a first-line treatment for patients with NPC resulted in a manageable safety profile and superior progression-free survival compared with GP alone. However, the treatment benefited only a subset of patients. Therefore, we evaluated response patterns in patients with NPC who were treated with programmed cell death protein 1 (PD-1) inhibitors to assess the influence of the tumor immune microenvironment on the efficacy of immunotherapies. Fifty NPC patients treated with PD-1 inhibitors at the Sun Yat-sen University Cancer Center were identified, and 50 and 28 samples were collected before and during treatment, respectively. mRNA expression levels of 289 tumor-immune-related genes were analyzed using the NanoString nCounter. Immune infiltration and correlations between clinical characteristics and the expression of immune-related genes were assessed. Tumors that responded to immunotherapy had significantly lower T helper 1 cell infiltration and higher chemokine signature scores compared with non-responding tumors. Notably, anti-PD-1 immunotherapy-responsive tumors had higher CXCR6 expression levels, suggesting that CXCR6 may be involved in the immune surveillance of NPC and in shaping the tumor microenvironment (TME). In addition, significant differences in the TME were observed between pre-treatment and treatment samples. Overall, CXCR6 expression was identified as a predictive biomarker for response to immunotherapy in NPC.

Keywords

CXCR6 / Immunotherapy / Tumor immune microenvironment / Toripalimab / Nasopharyngeal carcinoma / Programmed cell death protein 1 inhibitors

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