CD47 overexpression is common in intestinal non-GCB type diffuse large B-cell lymphoma and associated with 18q21 gain.

The CD47/SIRPα pathway is an emerging immune checkpoint that is a new therapeutic target. We investigated CD47 expression in DLBCL of various subtypes and organs. Moreover, the relationship between CD47 expression and genetic alterations was analyzed using panel-based massively parallel sequencing (NGS). CD8, CD68, and CD47 immunohistochemical staining were performed on 238 DLBCL patients. CD47 was scored according to intensity on a 5-level scale, and CD8 and CD68 were quantitatively evaluated using QuPath software. Panel based NGS was performed in 37 patients. In CD8 and CD68 quantitative analyses by organs, intestinal DLBCL showed significantly lower cytotoxic T-cell infiltration than that in others (P<0.001). The CD47-high group comprised 24 of 58 (41.4%) in DLBCL from intestine and 15 of 180 (8.3%) in DLBCL from other organs (P<0.001). The 18q21 gain/amplification was found in 10 of 37 patients, and all of them were CD47-high. Intestinal CD47-high DLBCL occurred in terminal ileum to ascending colon, and was restricted to non-germinal center B-cell type. In the survival analyses, the prognosis of non-intestinal CD47-high DLBCL was poorer than that of intestinal CD47-high DLBCL (P=0.025). CD47-high DLBCL was closely associated with 18q21 gain/amplification and showed a high prevalence in intestine. We propose to classify CD47-high DLBCL into intestinal and non-intestinal type. Further studies are necessary to assess whether the constellation of features seen here is reproducible and sufficient to consider primary intestinal DLBCL as a distinct biological entity.