Increase of programmed death-1-expressing intratumoral CD8 T cells predicts a poor prognosis for nasopharyngeal carcinoma

Intratumoral cytotoxic T lymphocytes are critical for controlling tumor recurrence, and programmed death-1 (PD-1) is a recognized marker of T-cell dysfunction. We analyzed this marker and its binding ligands in nasopharyngeal tumor tissue and non-cancerous nasopharyngeal control tissue to retrospectively evaluate the correlation between its expression and the post-treatment outcome of nasopharyngeal carcinoma patients. Using double immunofluorescence staining, we found that the expression of PD-1 in CD8 T cells in tumor tissue was significantly higher than in control tissue (mean: 28.4 vs 3.9%, P<0.0001). Although the expression rate of PD-1 in intratumoral CD8 cells was not associated with the other clinicopathological parameters examined, the higher expression rate in this subset of T cells significantly correlated with a poorer prognosis of overall survival, disease-free survival, and locoregional recurrence-free survival of the cancer patients (P=0.05, 0.007, and 0.004, respectively). Multivariate analysis confirmed it as an independent risk factor for death, treatment failure, and local recurrence of nasopharyngeal carcinoma. On the other hand, the expression of PD-1 in CD4 T cells and of its ligands in epithelial and stromal cells was not significantly different between tumor and control tissue, and its expression was not associated with clinical outcome of the cancer patients. We propose that PD-1 expression in CD8 cells reflects the selective suppression of cytotoxic lymphocytes in the tumor microenvironment and predicts recurrence of nasopharyngeal carcinoma after conventional therapies. Modern Pathology (2010) 23, 1393-1403; doi:10.1038/modpathol.2010.130; published online 23 July 2010