Immunotherapy of Hodgkin Lymphoma: Mobilizing the Patient's Immune Response

Classic Hodgkin lymphoma has a unique tumor composition in that there is a paucity of malignant cells present, and most of the tumor consists of normal immune and stromal cells. Despite the presence of an immune infiltrate within the tumor microenvironment, the malignant cells effectively evade the immune system and appear to utilize the presence of immune cells to promote the growth and survival of Hodgkin-Reed-Sternberg cells. Hodgkin-Reed-Sternberg cells evade immune detection because of overexpression of programmed death 1 ligands, PD-L1 and PD-L2, which suppress T-cell activation, and loss of expression of major histocompatibility complex molecules that prevent effective immune recognition. Recognition of these immune defects has led to clinical use of immune checkpoint blockade in classic Hodgkin lymphoma. Clinical trials using antibodies that block programmed death 1/PD-L1 signaling have shown remarkable responses to therapy and have led to the approval of nivolumab and pembrolizumab for use in patients with relapsed and refractory disease. Trials are currently testing immune checkpoint blockade in earlier lines of therapy.