The relationship between clinical prognostic factors, microvascular density, and tumor-infiltrating lymphocytes with CD47 and SIRPα expression in diffuse large B cell lymphomas

Aydan Kılıçarslan; Sevdenur Özdüzgün Polat; Hayriye Tatlı Doğan; Tuğba Dilay Kökenek Ünal; Şefika Karabulut; Gülsüm Özet

doi:10.1016/j.leukres.2024.107636

The relationship between clinical prognostic factors, microvascular density, and tumor-infiltrating lymphocytes with CD47 and SIRPα expression in diffuse large B cell lymphomas

Leuk Res. 2024 Dec 19:149:107636. doi: 10.1016/j.leukres.2024.107636. Online ahead of print.

Authors

Aydan Kılıçarslan¹, Sevdenur Özdüzgün Polat², Hayriye Tatlı Doğan³, Tuğba Dilay Kökenek Ünal³, Şefika Karabulut⁴, Gülsüm Özet⁵

Affiliations

¹ Ankara Yıldırım Beyazıt University, Pathology Clinic, Ankara, Turkey. Electronic address: dr.kilicaydan@gmail.com.
² Ankara City Hospital, Pathology Clinic, Ankara, Turkey.
³ Ankara Yıldırım Beyazıt University, Pathology Clinic, Ankara, Turkey.
⁴ Gulhane Department of Microbiology, Virology, Health Sciences University, Ankara, Turkey.
⁵ Ankara Yıldırım Beyazıt University, Hematology Clinic, Ankara, Turkey.

PMID: 39732044
DOI: 10.1016/j.leukres.2024.107636

Abstract

CD47 interacts with signal regulatory protein alpha (SIRPα) on macrophages to deliver an anti-phagocytic signal, enabling tumor cells to evade immune destruction. This study explores the relationship between CD47 and SIRPα expression and key clinical prognostic factors, microvascular density (MVD), and tumor-infiltrating lymphocytes (TIL) in Diffuse Large B Cell Lymphoma (DLBCL) cases. We analyzed tissue samples from 122 DLBCL cases using tissue microarray (TMA) blocks and immunohistochemical staining for CD47, SIRPα, CD31, and CD3. CD47 expression was scored using the Allred scoring system, and SIRPα expression was quantified based on the percentage of positive membranous and cytoplasmic expression. Clinical data, including IPI scores, relapse rates, and gene expression profiles, were correlated with the immunohistochemical findings.CD47 expression score ≥ 6 was significantly associated with the DLBCL-ABC phenotype (p = 0.029), higher IPI scores (p = 0.020), and increased relapse rates (p = 0.021). High SIRPα expression (≥25 % staining) was also linked to the ABC phenotype (p = 0.022) and frequent relapses (p = 0.021). Notably, cases with high microvascular density exhibited lower SIRPα expression (p = 0.013). There was no significant relationship between MVD and CD47 or other clinical prognostic factors. Additionally, higher CD3-positive TIL percentages were inversely correlated with IPI scores (p = 0.005), although no significant association was found between CD3 and CD47-SIRPα. The study reveals that increased CD47-SIRPα expression is partially linked to adverse prognostic indicators and reduced MVD in DLBCL cases. These findings suggest that targeting the CD47-SIRPα axis could offer a novel therapeutic approach in DLBCL, particularly for patients with poor prognostic features.

Keywords: CD47; Diffuse Large B Cell Lymphoma; Microvascular density; SIRPα; Tumor-infiltrating lymphocytes(TIL).