Checkpoint CD47 expression in classical Hodgkin lymphoma

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  • Alex Reza Gholiha
  • Peter Hollander
  • Liza Löf
  • Ingrid Glimelius
  • Gustaf Hedstrom
  • Daniel Molin
  • Hjalgrim, Henrik
  • Karin E. Smedby
  • Jamileh Hashemi
  • Rose Marie Amini
  • Gunilla Enblad

The glycoprotein CD47 regulates antiphagocytic activity via signal regulatory protein alpha (SIRPa). This study investigated CD47 expression on Hodgkin and Reed–Sternberg (HRS) cells in the classical Hodgkin lymphoma (cHL) tumour microenvironment and its correlation with prognosis, programmed-death (PD) immune markers, and SIRPa+ leukocytes. We conducted immunohistochemistry with CD47 and SIRPa antibodies on diagnostic biopsies (tissue microarrays) from cHL patients from two cohorts (n = 178). In cohort I (n = 136) patients with high expression of CD47 on HRS cells (n = 48) had a significantly inferior event-free survival [hazard ratio (HR) = 5.57; 95% confidence interval (CI), 2.78–11.20; p < 0.001] and overall survival (OS) (HR = 8.54; 95% CI, 3.19–22.90; p < 0.001) compared with patients with low expression (n = 88). The survival results remained statistically significant in multivariable Cox regression adjusted for known prognostic factors. In cohort II (n = 42) high HRS cell CD47 expression also carried shorter event-free survival (EFS) (HR = 5.96; 95% CI, 1.20–29.59; p = 0.029) and OS (HR = 5.61; 95% CI, 0.58–54.15; p = 0.136), although it did not retain statistical significance in the multivariable analysis. Further, high CD47 expression did not correlate with SIRPa+ leukocytes or PD-1, PD-L1 and PD-L2 expression. This study provides a deeper understanding of the role of CD47 in cHL during an era of emerging CD47 therapies.

Original languageEnglish
JournalBritish Journal of Haematology
Volume197
Issue number5
Pages (from-to)580-589
ISSN0007-1048
DOIs
Publication statusPublished - 2022

Bibliographical note

Funding Information:
We wish to give special thanks to Anders Berglund, PhD in medical epidemiology and biostatistics, and senior medical statistic consultant at Statistikakademin AB, Uppsala, for discussions and statistical calculations.

    Research areas

  • CD47, Hodgkin lymphoma, lymphoma, SIRPa, tumour markers

ID: 310965090