High CD47 Expression on HRS Cells Carries Poor Survival Implications in Classical HL

Amid the emergence of cluster of differentiation 47 (CD47)-targeted treatments for classical Hodgkin lymphoma (cHL), new insights offer a better understanding of the implications of the glycoprotein in the disease.

Retrospective findings, coming from 2 cohorts of patient biopsies undergoing immunohistochemistry with CD47 and SIRPa antibodies, show that CD47 expression on Hodgkin and Reed–Sternberg (HRS) cells varied between patients and was associated with poor outcomes.

This new study was published in British Journal of Haematology.

In a cohort of 136 patients, high expression of CD47 on HRS cells—observed in 48 patients—had negative implications for survival, with significantly poorer event-free (EFS; HR, 5.57) and overall survival (OS; HR, 8.54) compared with patients with low expression of the glycoprotein. This finding remained significant in a multivariable analysis. According to the researchers, this suggests the CD47 checkpoint pathway is critical for tumor surveillance escape in the disease, even in the absence of CD47 inhibition. The group noted that these findings are consistent with previous research.

“Interestingly, CD47 expression did not correlate with several investigated immune cells and programmed-death checkpoint markers. Moreover, SIRPa+ leukocytes lacked a significant correlation with CD47 expression levels or EFS and OS. However, the presence of SIRPa+ leukocytes correlated with increased proportions of PDL-L1+ leukocytes and PD-L1+ HRS cells,” commented the researchers. “These findings add to current understanding of the role of CD47 in cHL during an era of increased need for personalized medicine and ongoing trials targeting CD47 in several malignancies.”

In the second cohort, 16 patients (38%) had a high expression of CD47 on HRS cells, while 26 (62%) did not. Having a high expression of CD47 was associated with poorer EFS (HR, 5.96) but did not have a significant effect on HS (HR, 5.61). In multivariable analyses among this cohort, high expression on HRS cells was not statistically significantly associated with survival.

Across both groups, patients who had a high expression of CD47 on HRS cells exhibited significantly lower hemoglobin and lower albumin. They were also older and had higher erythrocyte sedimentation rate.

“A biological explanation for these associations is still uncertain. A link between associated inflammatory parameters and high expression of CD47 on HRS cells could be due to pluripotent cytokines that can both promote inflammation and upregulate CD47 in tumor cells,” wrote the authors. “The lack of correlation of CD47 protein expression and PD1, PD-L1 and PD-L2 was unexpected since a study has shown a correlation between PD-L1 mRNA and CD47 mRNA levels in leukemic malignancies. However, in this same study, no correlation between PD-L1 and CD47 protein expression was observed, consistent with current findings.”

The researchers found no statistically significant differences between CD47 expression on HRS cells based on clinical stage of disease, histological subtype, gender, tumor Epstein–Barr virus status, or presence of B symptoms.

Reference

Gholiha AR, Hollander P, Löf L, et al. Checkpoint CD47 expression in classical Hodgkin lymphoma. BR J Haematol. Published online March 17, 2022. doi:10.1111/bjh.18137