Characterization of Immunological Profiles with Clinical Significance in Patients with Classical Hodgkin Lymphoma

Introduction: Malignant classical Hodgkin lymphoma (cHL) cells express numerous immunoregulatory proteins that can shape their microenvironment and allow tumor cells to escape immune surveillance. Herein we aimed to characterize the immunological profile of cHL, and associate the findings with disease characteristics and outcome.

Patients and methods: We used NanoString digital gene expression profiling with the PanCancer Immune panel to assess the expression of 770 immune response genes in the tumor samples of 88 patients with primary cHL.

Results: The male/female ratio was 49%/51%, and the median age 32 years (range 16-85). Thirty-four (39%) patients were > 45 years, 66 (75%) had nodular sclerosis subtype and 46 (53%) stage III-IV disease. At the median follow-up of 42 months (range 12 to 164), 25 (28%) patients had relapsed and 10 (11%) died. Recurrence free survival (RFS) and overall survival (OS) rates at three years were 73% and 93%, respectively.

Unsupervised hierarchical clustering revealed five clusters of genes with differential expression between the patients. The clusters were enriched for the genes related to focal adhesion and extracellular matrix (ECM) interactions, Toll-like receptor signaling pathway, T-cell signaling, JAK-STAT signaling, and antigen processing and presentation. Interestingly, focal adhesion/ECM interaction and T-cell signaling signatures correlated with outcome. According to Kaplan-Meier estimates, the group of patients (n=14) with high expression of focal adhesion and ECM interaction signature genes had a 3-year RFS of 93% in comparison to 69% for those (n=74) with lower expression ( p = 0.073). In addition, a significant unfavorable impact of low expression of T-cell signature on RFS was observed among the subgroup of patients over 45 years (44% vs 87%, p=0.003). Baseline characteristics, including gender, age, histological subtype and stage were equally distributed in all subgroups.

Conclusion: Our data reveal biologically relevant immunological profiles, and association of focal adhesion/ECM interaction and T-cell signaling signatures with treatment resistance in patients with primary cHL. A detailed characterization of immune cell composition in the cHL microenvironment and its impact on survival is ongoing.