Clinical significance of signal regulatory protein alpha (SIRPα) expression in esophageal squamous cell carcinoma

Signal regulatory protein alpha (SIRP alpha) is a type I transmembrane protein that inhibits macrophage phagocytosis of tumor cells upon interaction with CD47, and the CD47-SIRP alpha pathway acts as an immune checkpoint factor in cancers. This study aims to clarify the clinical significance of SIRP alpha expression in esophageal squamous cell carcinoma (ESCC). First, we assessed SIRP alpha expression using RNA sequencing data of 95 ESCC tissues from The Cancer Genome Atlas (TCGA) and immunohistochemical analytic data from our cohort of 131 patients with ESCC. Next, we investigated the correlation of SIRP alpha expression with clinicopathological factors, patient survival, infiltration of tumor immune cells, and expression of programmed cell death-ligand 1 (PD-L1). Overall survival was significantly poorer with high SIRP alpha expression than with low expression in both TCGA and our patient cohort (P P = .027, respectively). High SIRP alpha expression was associated with greater depth of tumor invasion (P = .0017). Expression of SIRP alpha was also significantly correlated with the tumor infiltration of M1 macrophages, M2 macrophages, CD8(+) T cells, and PD-L1 expression (P < .001, P < .001, P = .03, and P < .001, respectively). Moreover, patients with SIRP alpha/PD-L1 coexpression tended to have a worse prognosis than patients with expression of either protein alone or neither. Taken together, SIRP alpha indicates poor prognosis in ESCC, possibly through inhibiting macrophage phagocytosis of tumor cells and inducing suppression of antitumor immunity. Signal regulatory protein alpha should be considered as a potential therapeutic target in ESCC, especially if combined with PD-1-PD-L1 blockade.