Activating the Antitumor Immune Response in Non-Hodgkin Lymphoma Using Immune Checkpoint Inhibitors

Non-Hodgkin lymphomas comprise a heterogenous group of disorders which differ in biology. Although response rates are high in some groups, relapsed disease can be difficult to treat, and newer approaches are needed for this patient population. It is increasingly apparent that the immune system plays a significant role in the propagation and survival of malignant cells. Immune checkpoint blocking agents augment cytotoxic activity of the adaptive and innate immune systems and enhance tumor cell killing. Anti-PD-1 and anti-CTLA-4 antibodies have been tested as both single agents and combination therapy. Although success rates with anti-PD-1 antibodies are high in patients with Hodgkin lymphoma, the results are yet to be replicated in those with non-Hodgkin lymphomas. Some lymphoma histologies, such as primary mediastinal B cell lymphoma (PMBL), central nervous system, and testicular lymphomas and gray zone lymphoma, respond favorably to PD-1 blockade, but the response rates in most lymphoma subtypes are low. Other agents including those targeting the adaptive immune system such as TIM-3, TIGIT, and BTLA and innate immune system such as CD47 and KIR are therefore in trials to test alternative ways to activate the immune system. Patient selection based on tumor biology is likely to be a determining factor in treatment response in patients, and further research exploring optimal patient populations, newer targets, and combination therapy as well as identifying biomarkers is needed.