Role of Circulating Myeloid-Derived Suppressor Cell (MDSC) in Hodgkin Lymphoma (HL) Progression: Highlighting Clinical Relevance

Abstract

Introduction. About 15-25% of patients with HL have primary refractory disease or relapse after the first line of therapy and about half of them diagnosed chemosensitivity after transplantation. In the attempt to find a peripheral blood biological marker that could mirror the dysregulated microenvironment of HL, we analyzed the number of myeloid-derived suppressor cells (MDSC) and its correlation with clinical variables and response to therapy. Methods. 52 primary HL patients, (median age: 40, range: 19-61 years; male: 21, female: 31), were included in the study since April, 2018. 63.5% and 36.5% of patients have been diagnosed with early and advanced stages of HL, respectively, and received the ABVD or BEACOPP (14/esc) as a 1st-line treatment regimen. We have also used a routine protocol of metabolic PET assessment according to Deauville criteria of treatment response. Results. 82.6% (43/52) of patients achieved remission (CR/PR) during the follow-up period (median timeline: 25 months). We recorded a disease progression in 6/52 (11.5%) patients during and after the 1st line therapy, (median time to relapse - 8 months). We observed that the level of E-MDSC in patients with HL before treatment is twelve times higher than in healthy control group (24% vs 2 % respectively, p=0.02). Also, the E-MDSC count increases significantly with age of HL patient (with the highest levels in patients over 40 y.o., p=0.008) and with the stage of the disease. Thus patients with advanced stages (III-IV) of HL have increased % of circulating E-MDSC compared to early stages (1A-2B) of disease (p=0.07) . We also found the significant correlation between increased level of MDSC during the treatment and the presence of 4 or more risk factors by IPS (p=0.03). Patients with negative PET results (interim and EOT) had a significantly lower percent of E-MDSC in peripheral blood during and in the end of treatment compare to positive PET patients (interim MDSC: 14% vs 36%, p=0.03; EOT MDSC: 12% vs 42%, p=0.0007, respectively). Patients with CR also had increased number of T and NK-T cells compared to pre-treatment numbers (p=0.05), which all together indicates the activation of anti-tumor immune response. Conclusion. Increased level of circulating E-MDSC is associated with age, advanced stage of HL, presence of 4 or more IPS risk factors and poor clinical outcome. Evaluation of MDSC levels in peripheral blood can be used as additional prognostic marker for early clinical outcome assessment. The discovery of new prognostic factors will improve the individualized approach to the treatment of patients and reduce the risk of disease recurrence.