Combination of CD47 and signal-regulatory protein-α 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 (SIRP alpha) inhibits phagocytosis, thus affecting the clinical outcomes of neoplastic diseases. Although CD47 upregulation is associated with poor prognosis in several malignancies, the effect of SIRP alpha expression and its coexpression with CD47 remains unclear. This study aimed to investigate the clinicopathologic effect of CD47 and SIRP alpha expression in diffuse large B-cell lymphoma (DLBCL). Immunostaining of 120 biopsy samples showed that CD47 is primarily expressed in tumor cells, whereas SIRP alpha is expressed in nonneoplastic stromal cells, mostly macrophages. CD47(high)cases showed higher MYC protein expression and lowerMYCtranslocation. The SIRP alpha(high)cases presented significantly shorter overall survival (OS) and progression-free survival (PFS) than SIRP alpha(low)cases in the activated B-cell (ABC) subtype of DLBCL (P = .04 andP = .02, respectively). Both CD47(high)and SIRP alpha(high)presented significantly shorter OS and PFS than other cases among all DLBCL patients (P = .01 andP = .004, respectively), and the ABC type (P = .04 andP = .008, respectively) but not the germinal center B-cell type. Both CD47(high)and SIRP alpha(high)yielded a constant independent prognostic value for OS and PFS in multivariate analysis (hazard ratio [HR], 2.93; 95% confidence interval [CI], 1.20-7.43;P = .02; and HR, 2.87; 95% CI, 1.42-5.85;P = .003, respectively). To the best of our knowledge, this is the first study to report that combinatorial CD47 and SIRP alpha expression is a potential independent prognostic factor for DLBCL. Evaluation of CD47 and SIRP alpha expression could be useful before CD47 blockade therapy.