Overexpression of HHLA2, a member of the B7 family, is associated with worse survival in human colorectal carcinoma

Colorectal carcinoma (CRC) is one of the most common malignancies, and immunotherapy has opened a new field of cancer treatment in recent years. Generally, CRC does not benefit from immunotherapy. HHLA2, a member of the B7 family, is a novel immune checkpoint molecule, and the prognostic value of HHLA2 in CRC patients and the association between HHLA2 expression and clinicopathological characteristics remains unknown. Materials and

HHLA2 expression is upregulated in CRC patients, and HHLA2 is an independent prognostic factor of overall survival of CRC patients. High HHLA2 expression is closely correlated with CD8 T-cell infiltration status and can predict poor prognosis in CRC patients.

This study included 63 patients diagnosed with CRC, and their resected specimens were obtained and constructed as a tissue microarray. Expression of HHLA2 and CD8 was detected by the double immunohistochemistry method. Based on follow-up data, correlations of HHLA2 expression and clinicopathological features, including overall survival, in CRC patients were evaluated.

High HHLA2 expression was detected in CRC tumor tissues, compared to the adjacent noncancerous tissues. HHLA2 expression level was significantly related to the depth of invasion (P=0.044) and CD8+ T-cell infiltration status (P=0.016), and predicted high mortality rate (P=0.035). HHLA2 acted as an independent predictive factor in the overall survival of CRC patients (P=0.039, hazard ratio=2.162, 95% CI 1.041-3.084).