Altered profile of immune regulatory cells in the peripheral blood of lymphoma patients

Abstract

Background Regulatory immune cells may modulate the lymphoma microenvironment and are of great interest due to the increasing prevalence of treatment with immunotherapies in lymphoma patients. The aim was to explore the composition of different immune regulatory cell subsets in the peripheral blood of newly diagnosed lymphoma patients in relation to treatment outcome. Methods Forty-three newly diagnosed patients with lymphoma were included in the study; 24 with high-grade B-cell lymphoma (HGBCL) and 19 with classical Hodgkin lymphoma (cHL). Peripheral blood was prospectively collected and immune regulatory cells were identified by multi-color flow cytometry and analyzed in relation to healthy blood donors and clinical characteristics and outcome. Results The percentage of CD3-positive T-cells was lower ( p = 0.03) in the peripheral blood of lymphoma patients at diagnosis compared to healthy blood donors regardless of lymphoma subtype, although statistically, neither the percentage of monocytes ( p = 0.2) nor the T-cell/monocyte ratio ( p = 0.055) differed significantly. A significant decrease in the percentage of a subset of regulatory NK cells (CD7 + /CD3 − /CD56 bright /CD16 dim/− ) was identified in the peripheral blood of lymphoma patients compared to healthy blood donors ( p = 0.003). Lymphoma patients also had more granulocytic myeloid-derived suppressor cells (MDSCs) (p = 0.003) compared to healthy blood donors, whereas monocytic MDSCs did not differ significantly ( p = 0.07). A superior disease-free survival was observed for cHL patients who had an increase in the percentage of granulocytic MDSCs ( p = 0.04). Conclusions An altered profile of immune cells in the peripheral blood with a decrease in T-cells and regulatory NK-cells was observed in newly diagnosed lymphoma patients. CHL patients with higher percentages of regulatory NK cells and higher percentages of granulocytic MDSCs might have a better outcome, although the number of patients was low. Electronic supplementary material The online version of this article (10.1186/s12885-019-5529-0) contains supplementary material, which is available to authorized users.

Monocytic Myeloid Derived Suppressor Cells in Hematological Malignancies

“…Our group showed that three MDSCs subtypes, including CD14+HLA-DR-mo-MDSCs, were increased in newly-diagnosed advanced-stage HL patients and reduced after two and six cycles of ABVD chemotherapy [20]; similarly, in relapsed/refractory patients, several MDSCs subtypes, including mo-MDSCs, were increased at time of disease progression and reduced after treatment with brentuximab vedotin [19]. However, immune-suppressive effect and correlation with outcome is stronger for g-MDSCs than mo-MDSCs in HL [20,38,39]. Another study demonstrated that g-MDSCs were increased in both HL and B-cell NHL patients and correlated significantly with unfavorable prognostic index scores and an inferior outcome [38].…”

“…Another study demonstrated that g-MDSCs were increased in both HL and B-cell NHL patients and correlated significantly with unfavorable prognostic index scores and an inferior outcome [38]. In a third small series, only g-MDSCs (but not mo-MDSCs) were increased in HL patients compared to healthy controls [39].…”

Advancing CAR T-Cell Therapy for Solid Tumors: Lessons Learned from Lymphoma Treatment

“…Patients received neither immunosuppressive therapy nor chemotherapy for at least 3 months; thus, the percentages seem to reflect their constant immune status. In contrast to this, a recent study has compared proportions of suppressor cell subpopulations in lymphoma patients (n = 43) and healthy donors [100]. No significant difference in Treg populations between the groups was observed, although some non-T-cell populations (MDSC and NK regulatory cells) were elevated in the patients.…”

“…No significant difference in Treg populations between the groups was observed, although some non-T-cell populations (MDSC and NK regulatory cells) were elevated in the patients. The above-studied cohorts were similar (Europeans,~60 years), however direct comparison of the results cannot be totally correct due to variations in applied methodology: (1) calculation of Treg percentages in total population of PBMCs [100] or blood cells [99]; and (2) different definition of Treg phenotypes. Some studies on lymphoma patients have similarly found no variation in Treg levels in comparison to healthy volunteers [101,102], while others reported several-fold difference regardless of nationality, age and disease status (newly diagnosed vs. relapsed) [102][103][104].…”

Circulating Myeloid Regulatory Cells: Promising Biomarkers in B-Cell Lymphomas

“…This could be linked to an increase in monocytic myeloid derived suppressor cells (M-MDSC), as it has been suggested in DLBCL ( 20 , 31 ) and CLL, in which M-MDSC levels correlate with response to treatment ( 32 – 35 ). Concerning the granulocytic lineage, polymorphonuclear MDSC (PMN-MDSC) have been proposed as a marker of poor prognosis in DLBCL ( 36 ), but other works did not find any association between PMN-MDSC and DLBCL prognosis ( 31 , 37 ). In HL, the presence of a CD34 pos MDSC subtype in the blood has been associated with worsened prognosis ( 38 ).…”