Absolute Count of Myeloid Derived Suppressor Cells (MDSC) Is Able to Predict the Response to Early-PET In Hodgkin Lymphoma

Abstract 3882

Inflammation dominates both the histological and the clinical pictures of Hodgkin's Lymphoma (HL) and there are several clues that accessory cells (neutrophils, macrophages, and lymphocytes) have an important role in the development and progression of the disease.

Recent studies have also highlighted the importance of interim PET (after 2 cycles of chemotherapy) as the most important prognostic factor for HL. Indeed, the positivity of interim PET is linked to the persistence of the reactive microenvironment that promotes tumor cells survival.

CD68+ tumour associated macrophages have been recently identified as new marker of disease and their putative progenitors in peripheral blood are identified as Myeloid Derived Suppressor Cells (MDSC). This subpopulation of cells has been studied in some solid tumors where it has been documented its ability to suppress T-cell immune responses by several mechanisms, including expression of arginase and nitric oxide synthase.

In order to identify an additional HD marker with prognostic significance, we evaluated 35 HL patients for circulating levels of MDSC, identified as CD34⁺, CD45⁺, CD11b⁺, CD13⁺, CD14^- in peripheral blood by flow cytometry at diagnosis and correlated lab findings to clinical features and response to early 18FDG-PET, performed after the 2^nd cycle.

We found that at diagnosis HL patients have higher levels of circulating MDSC when compared to matched for sex and age healthy controls (mean 3,66 ± 1,94/mmc vs 1,69 ± 0,87/mmc, p=0.0001).

Absolute number of MDSC was not correlated to markers of inflammation (ferritin, ESR, CRP,) tumor burden (stage, IPS, presence of bulky disease) and SUV at diagnosis PET. However, an interesting correlation was found between MDSC count at diagnosis and positivity of interim PET: all patients with a positive interim PET (5/35) had increased MDSC count at diagnosis and 5/7 patients with a count larger than 4.5 cells/uL had a positive early PET, with documented progression/relapse of disease for 4 of them.

In order to confirm the immunosuppressive abilities of MDSC, we co-cultured myeloid cells (isolated by CD33⁺ or CD66⁺) from three HL patients, together with lymphocytes obtained by Ficoll-Hypaque from healthy donors and we found that lymphocytes were unable to become effectors after stimulation with PMA as documented by reduction of CD25, CD69 expression and increase of CD62L in comparison with control lymphocytes incubated with PHA alone.

In conclusion, MDSC 1) are increased in peripheral blood of HL patients at diagnosis 2) correlate with interim PET 3) have a strong prognostic value, that is earlier and more easily accessible than interim PET 4) represent a paradigma of how a myeloid compartment may favour the development of a lymphoid neoplasia through T-cell impairment.