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

The CD47/signal regulatory protein α pathway is an emerging immune checkpoint that is a new therapeutic target. We investigated CD47 expression in diffuse large B-cell lymphoma (DLBCL) of various subtypes and organs. Moreover, the relationship between CD47 expression and genetic alterations was analyzed using panel-based massively parallel sequencing (next-generation sequencing [NGS]). CD8, CD68, and CD47 immunohistochemical staining were performed on 238 patients with DLBCL. 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 < .001). The CD47-high group comprised 24 of 58 (41.4%) patients in the group with DLBCL from intestine and 15 of 180 (8.3%) patients in the group with DLBCL from other organs (P < .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 nongerminal center B-cell type. In the survival analyses, the prognosis of nonintestinal CD47-high DLBCL was poorer than that of intestinal CD47-high DLBCL (P = .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 nonintestinal types. 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.