Development and validation of an immune checkpoint-based signature to predict prognosis in nasopharyngeal carcinoma using computational pathology analysis

BACKGROUND: Immunotherapy, especially immune checkpoint inhibition, has provided powerful tools against cancer. We aimed to detect the expression of common immune checkpoints and evaluate their prognostic values in nasopharyngeal carcinoma (NPC). METHODS: The expression of 9 immune checkpoints consistent with 13 features was detected in the training cohort (n = 208) by immunohistochemistry and quantified by computational pathology. Then, the LASSO cox regression model was used to construct an immune checkpoint-based signature (ICS), which was validated in a validation cohort containing 125 patients. RESULTS: High positive expression of PD-L1 and B7-H4 was observed in tumour cells (TCs), whereas PD-L1, B7-H3, B7-H4, IDO-1, VISTA, ICOS and OX40 were highly expressed in tumour-associated immune cells (TAICs). Eight of the 13 immune features were associated with patient overall survival, and an ICS classifier consisting of 5 features (B7-H3TAIC, IDO-1TAIC, VISTATAIC, ICOSTAIC, and LAG3TAIC) was established. Patients with high-risk scores in the training cohort had shorter overall (P < 0.001), disease-free (P = 0.002), and distant metastasis-free survival (P = 0.004), which were confirmed in the validation cohort. Multivariate analysis revealed that the ICS classifier was an independent prognostic factor. A combination of the ICS classifier and TNM stage had better prognostic value than the TNM stage alone. In addition, the ICS classifier was significantly associated with survivals in patients with high EBV-DNA load. CONCLUSIONS: We determined the expression status of nine immune checkpoints consistent with 13 features in NPC and further constructed an ICS prognostic model, which might add prognostic value to the TNM staging system.