CD39-Expressing CD8(+) T Cells as a New Molecular Marker for Diagnosis and Prognosis of Esophageal Squamous Cell Carcinoma

SIMPLE SUMMARY: Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers in the world with an insidious onset and poor prognosis. Studies have reported that CD39 is highly expressed on several human tumors and is closely associated with CD8(+) T cells in the tumor microenvironment. We aimed to explore the effect of CD39 expression on CD8(+) T cells and on the diagnosis and prognosis of ESCC by analyzing 95 ESCC samples in order to better predict the probability of patients’ survival by establishing a nomogram model. We observed that CD39 expression was higher on CD8(+) T cells in cancer tissues. High CD39-expressing CD8(+) T cells were an independent risk factor for the prognosis of ESCC, and its expression was significantly positively correlated with the expression of PDCD1, CTLA4, and HAVCR2. It is further proposed that the restoration of partially exhausted CD8(+) T cells by inhibiting CD39 may be a new strategy for treating ESCC. ABSTRACT: We aimed to explore the effect of CD39 expression on CD8(+) T cells and on the diagnosis and prognosis of esophageal squamous cell carcinoma (ESCC). The independent prognostic factors for the surgical specimens of the 95 ESCC patients were screened by multivariate Cox regression analysis. Differential gene expression analysis was performed by the NetworkAnalyst platform based on data from the Gene Expression Omnibus (GEO). The expression of CD39 on CD8(+) T cells in the CK(+) region was higher in cancer tissue than in paracancerous tissue (p = 0.011), and high CD39-expressing CD8(+) T cells in the CK(+) region (HR, 2.587; p = 0.033) and high CD39-expressing CD8(+) T cells in the CK(−) region (HR, 3.090; p = 0.008) were independent risk factors for prognosis in ESCC patients; the expression of ENTPD1 was upregulated in ESCC tissues compared to normal tissues (adjusted p < 0.001; log(2) fold change = 1.99), and its expression was significantly positively correlated with the expression of PDCD1, CTLA4, and HAVCR2. High CD39-expressing CD8(+) T cells can be used as a new molecular marker for the diagnosis and prognosis of ESCC, and the restoration of partially exhausted CD8(+) T cells by inhibiting CD39 may be a new strategy for treating ESCC.