The translational science of hodgkin lymphoma

Abstract

Summary Hodgkin Lymphoma (HL) is an unusual B‐cell lymphoma because the malignant cells exist as a minority population in a densely cellular microenvironment. The microenvironment is comprised predominately of inflammatory and immune cells with fibrosis in some cases. There are multiple dysregulated signalling pathways that sustain HL within this microenvironment, such as the Nuclear factor‐κB and Janus kinase/signal transducers and activators of transcription pathways. Advances in genomic medicine have enabled a better characterisation of the rare tumour cells and improved our understanding of the signalling mechanisms that exist between the malignant cell and its microenvironment. Current therapy for HL produces excellent clinical outcomes in most younger patients. However, problems with current treatment approaches include poorer outcomes in the elderly, toxicity of highly‐effective combination chemotherapy regimens and relapse in high‐risk patients. Better understanding of disease biology aids in upfront prognostication of patients, defines new methods for treatment monitoring and assists in the recognition of novel targets for therapy. Biology‐driven therapies, including anti‐CD30 antibody conjugates, cellular immunotherapies and immune modulation, particularly with checkpoint inhibitors, have changed treatment algorithms for relapsed/refractory patients. Future challenges exist in incorporating immune‐based therapies earlier in treatment algorithms to reduce toxicity and prevent relapse for patients with HL.

The role of trogocytosis in immune surveillance of Hodgkin lymphoma

“… 5 , 6 Their complex interactions within the HL microenvironment have been well summarized and discussed. 5 – 8 This review will focus on the contribution of trogocytosis, 9 , 10 also called transendocytosis, 11 to the establishment of the immunosuppressive microenvironment in HL.…”

Formation of the Immunosuppressive Microenvironment of Classic Hodgkin Lymphoma and Therapeutic Approaches to Counter It

“…Despite a great inflammatory infiltrate, patients with cHL have an impaired cellular immune response [107,142]. This is mediated by several factors including the high expression of PD-L1 and PD-L2 ligands by HRS cells, since PD-1 engagement by PD-L1 leads to T cell exhaustion, that is reduced T cell activation and proliferation [2,6] (Figure 1).…”

Brentuximab vedotin in association with bendamustine in refractory or multiple relapsed Hodgkin lymphoma. A retrospective real‐world study

“…In such patients, conventional chemotherapy results in very poor outcomes, allowing a median OS of around 25 months . Recently, a better understanding of the complex and unique cHL biology paved the way for the development of biology‐driven therapies and a few new drugs with remarkable efficacy and acting by diverse and novel mechanisms of action have become available in clinical practice . This scenario has ushered in a new treatment era and has opened new perspectives for improving the outcome of RR‐cHL patients .…”