Prognostic value of immune score in nasopharyngeal carcinoma using digital pathology

BACKGROUND: Tumor-infiltrating lymphocytes have been reported as prognostic markers in tumors. We aimed to assess the prognostic value of total T cell (CD3(+)) density, cytotoxic T cell (CD8(+)) density and memory T cell (CD45RO(+)) density in patients with nasopharyngeal carcinoma (NPC). METHODS: The expression of CD3, CD8 and CD45RO was detected by immunohistochemistry in the training (n=221) and validation cohorts (n=115). The densities of these three markers were quantified by digital pathology both in the tumor and stroma. Then, we developed the immune score based on the density of these three markers and further analyzed its prognostic value. RESULTS: The high density of CD3(+), CD8(+) and CD45RO(+) T cells both in the tumor and/or stroma were significantly associated with the decrease in mortality in the training cohort, respectively. High immune score predicted a prolonged overall survival (OS) (HR 0.34, 95% CI 0.18 to 0.64, p=0.001, disease-free survival (DFS) (HR 0.44, 95% CI 0.25 to 0.78, p=0.005) and distant metastasis-free survival (DMFS) (HR 0.43, 95% CI 0.21 to 0.87, p=0.018) in NPC patients. The findings were confirmed in the validation cohort. Multivariate analysis revealed that immune score remained an independent prognostic indicator for OS, DFS and DMFS. In addition, we established a nomogram with the integration of all independent variables to predict individual risk of death. CONCLUSIONS: We established an immune score model, which provides a reliable estimate of the risk of death, disease progress and distant metastasis in NPC patients.