Prognostic Markers within the Tumour Microenvironment in Classical Hodgkin Lymphoma

SIMPLE SUMMARY: Approximately one in seven patients with classical Hodgkin lymphoma have refractory disease or relapse after standard front line chemotherapy. Prognostic biomarkers could help determine candidates for more effective treatment. The latest advances in research techniques have contributed to new insights in understanding the tumour microenvironment of Hodgkin lymphoma and the crucial role it plays in the disease course and response to treatment. Many new potential biomarkers are being explored in this setting and the results of these studies, as well as diagnostic methodologies, are presented in this review. ABSTRACT: Classical Hodgkin lymphoma (cHL) accounts for 0.4% of all new cancer cases globally. Despite high cure rates with standard treatment, approximately 15% of patients still experience relapsed or refractory (RR) disease, and many of these eventually die from lymphoma-related causes. Exciting new targeted agents such as anti-PD-1 agents and brentuximab vedotin have changed the therapeutic paradigm beyond chemotherapy and radiotherapy alone. Advances in understanding of the molecular biology are providing insights in the context of novel therapies. The signature histology of cHL requires the presence of scant malignant Hodgkin Reed–Sternberg cells (HRSCs) surrounded by a complex immune-rich tumour microenvironment (TME). The TME cellular composition strongly influences outcomes, yet knowledge of the precise characteristics of TME cells and their interactions with HRSCs is evolving. Novel high-throughput technologies and single-cell sequencing allow deeper analyses of the TME and mechanisms elicited by HRSCs to propagate growth and avoid immune response. In this review, we explore the evolution of knowledge on the prognostic role of immune cells within the TME and provide an up-to-date overview of emerging prognostic data on cHL from new technologies that are starting to unwind the complexity of the cHL TME and provide translational insights into how to improve therapy in the clinic.