Combination of CD47 and SIRPalpha constituting the "don't eat me signal" is a prognostic factor in diffuse large B-cell lymphoma.

The interaction between CD47 and signal-regulatory protein alpha (SIRPalpha) inhibits phagocytosis, thus affecting the clinical outcomes of neoplastic diseases. Although CD47 upregulation is associated with poor prognosis in several malignancies, the effect of SIRPalpha expression and its co-expression with CD47 remains unclear. This study aimed to investigate the clinicopathological effect of CD47 and SIRPalpha expression in diffuse large B-cell lymphoma (DLBCL). Immunostaining of 120 biopsy samples showed that CD47 is primarily expressed in tumor cells, whereas SIRPalpha is expressed in non-neoplastic stromal cells, mostly macrophages. CD47(high) cases showed higher MYC protein expression and lower MYC translocation. SIRPalpha(high) cases presented significantly shorter overall survival (OS) and progression-free survival (PFS) than SIRPalpha(low) cases in the ABC subtype of DLBCL (P = 0.04 and P = 0.02, respectively). Both CD47(high) and SIRPalpha(high) presented significantly shorter OS and PFS than other cases among all DLBCL patients (P = 0.01 and P = 0.004, respectively), and the ABC type (P = 0.04 and P = 0.008, respectively) but not the GCB type. Both CD47(high) and SIRPalpha(high) yielded a constant independent prognostic value for OS and PFS in multivariate analysis (HR, 2.93; 95% CI, 1.20-7.43; P = 0.02, and HR, 2.87; 95% CI, 1.42-5.85; P = 0.003, respectively). To the best of our knowledge, this is the first study to report that combinatorial CD47 and SIRPalpha expression is a potential independent prognostic factor for DLBCL. Evaluation of CD47 and SIRPalpha expression may be useful before administration of CD47 blockade therapy.