Composition of Classical Hodgkin Lymphoma Microenvironment Is Associated with Clinical Outcome

Background.

Classical Hodgkin's lymphoma (cHL) is characterized by only few malignant cells and an abundance of inflammatory cells.cHL infiltrating cells produce cytokines and growth factors that provide essential stimulatory signals for survival and proliferation of Hodgkin and Reed-Sternberg (HRS) cells. Moreover, clinical behaviour of cHL may be directly regulated by the cross-talk between HRS cells and other cells in their microenvironment. The aim of our study was to estimate the role of microenvironmental composition in clinical outcome of cHL.

Methods.79 patients (pts) with cHL were included in this study (median age: 41, range: 18-65 years; males: 26, females: 53).Patients were treated with ABVD or BEACOPP (14/esc) and radiation therapy. CR/PR was achieved in 86.1% of patients. 13.9% of pts had relapse or disease progression during the therapy.

Using IHC and qPCR techniques, we analyzed lymph-node biopsy obtained from patients during diagnostic to determine cellular and cytokine signature (CD3, CD19, CD11b, PD-L1, PD-L2, IDO, TGF-β, IL-13) that correlates with cHL treatment outcome.

Results. Expression level of tested markers was heterogeneous across the samples and did not correlate with histological variant or stage of cHL. For most of cytokines as well as immunomodulatory molecules we did not notice significant independent effect on cHL clinical outcome, except IL-13, which appeared to be a strong and independent marker of cHL prognosis. High expression of IL-13 was associated with lower EFS and OS rates comparing to IL-13 low/negative group (p<0.05).

We found that the presence of myeloid CD11b+ cells in cHL microenvironment correlates significantly with shortened EFS rate (p<0.05). Multivariate analysis has shown that the negative impact of presence of myeloid cells increases gradually when combined with elevated expression of one or more following markers - PD-L1, IDO or TGF-β (p<0.05). At the same time, we did not find any significant associations between cHL outcome and B- or T-cells populations

Conclusion.In summary, our study showed the presence of CD11b+ myeloid cells together with increased expression of checkpoints molecules and cytokines (PDL1, IDO, TGF-β and IL-13)in diagnostic lymph-node samples is associated with cHL clinical outcome.