Hodgkin lymphoma: targeting the tumor microenvironment as a therapeutic strategy

Over the past decade, new biologic insights have revealed the key role of the tumor microenvironment in the pathogenesis of classical Hodgkin lymphoma (cHL). The primary Hodgkin Reed-Sternberg (HRS) tumor cells normally constitute less than 1% of the tumor cellularity in cHL, and are surrounded by an abundant and heterogeneous inflammatory infiltrate. The cross talk between the HRS cells and the cells of the cHL microenvironment sustains tumor growth and survival. An improved understanding of this phenomenon has led to the development of novel antitumor strategies that alter the cHL microenvironment, changing it from protective to cytotoxic. Developing new strategies remains a high priority because--despite the curability of cHL--as many as one-third of advanced-stage patients will relapse after first-line therapy. Furthermore, only half of relapsed patients will obtain long-term disease control through autologous stem cell transplant. In this review, we will provide an overview of the role of the cHL microenvironment in disease biology, the agents currently available or under investigation targeting the cHL microenvironment, and the most promising and innovative treatment platforms being evaluated in clinical trials.