Role of Circulating Myeloid-Derived Suppressor Cell (MDSC) in Hodgkin Lymphoma (HL) Patients: Prospective Study

Introduction. MDSC's are a heterogeneous population of bone marrow-derived myeloid progenitors including macrophages, granulocytes, dendritic cells and immature myeloid cells, which expand dramatically with tumour growth, and there are several clues have an important role in the disease progression. Recent studies have also highlighted interim PET as the most important prognostic factor for HL. The interim PET positivity may indicate that there is a reactive microenvironment promoting tumor cells survival. In this study we analyzed the prognostic significance of MDSC count together with PET in HL patients.

Methods. The 29 primary HL patients (median age: 33, range 19-61 years; males: 15, females: 14) were included in the study from Apr 2018 until now. 62% of patients were diagnosed with early stages of HL, while 38% - with advanced stages. ABVD or BEACOPP (14/esc) were administered as a 1st-line therapy.

Peripheral blood mononuclear cells (PBMC) were isolated on ficol density gradient from peripheral blood before treatment, interim after 2-3 chemotherapy cycles and after the end of treatment (EOT). The percentage of E-MDSCs subtype and lymphoid populations was measured by flow cytometry using CD11b, CD33, CD14, HLA-DR, CD34, CD45, CD3, CD4, Cd8, CD16, CD56 antibodies. Metabolic PET-CT imaging was performed to routine protocols using Deauville criteria for response assessment.

Results. 93% of patients achieved remission (CR/PR) during follow-up period (median 11.6 months). All pts are still in follow-up. The count of E-MDSC was increased in HL patients (median 12.5%) compared to matched for sex and age healthy controls (median 11%) and was higher in non-responders (median 19.7%). We also found that E-MSDC count in HL patients significantly increases with age - 6.5% in patients under 40 years vs 19.8% in patients 40+ years, p=0.007. No significant correlations were found between the frequency of MDSC and clinicopathological factors, including gender, Ann Arbor Stage, B symptoms, IPI scores.

The number of NK-T (CD3+CD16+CD56+) cells increased on 6.73 % after EOT compared to before treatment, p=0.009. Theoretically, this means that immunosuppression is reduced and the antitumor immune response of the body is improved.

93.1% (27/29) and 6.9% (2/29) of patients had 1-3 and 4-5 DS of the EOT, respectively (p < 0.05). We recorded one early relapse (11months) after the 1st line therapy - patient had high level of MDSCs before treatment and it remained high after iPET and EOT-PET.

Additionally, pts with iPET 4DS have a greater number of E-MDSCs compared to healthy control and, when complete remission is achieved, their values return to be equal to healthy control.

We found strong significant association between EOT-PET and level of E-MDSC after treatment. Thus, pts with EOT-PET-ve had lower expression E-MDSC vs EOT-PET+ve (3% vs 29% respectively, p=0.0007). May be in future it can be new prognostic factor for predict to relapse.

Conclusion. Patients with HL have high level of expression MDSC. Biomarkers research and HL biology at its basis may potentially rise up to the challenge of sole clinical prognostic factors application. This potentially area for research but are as yet unproven and in need have prospective validation.