Immunotherapy, particularly natural killer cell therapy, is garnering attention for treating lymphoma, due to the unique properties of natural killer cells, most importantly rapid and potent antitumor responses without prior sensitization. However, the tumor microenvironment and immune escape mechanisms can impair natural killer cell function in lymphoma. To address these challenges, researchers are exploring therapeutic interventions to restore or enhance their activity. Of the various approaches of cell therapy, such as allogeneic- or autologous-natural killer cell infusions, chimeric antigen receptor natural killer cells, and combination therapies, allogeneic natural killer cell transplantation has shown promise in specific subtypes of lymphoma, offering a reduced risk of graft-versus-host disease, improved response rates, prolonged remissions, and increased overall survival. Combining natural killer cell therapy with standard treatments such as chemotherapy or immune checkpoint inhibitors holds potential for synergistic effects. Nevertheless, addressing challenges such as cell persistence, the immunosuppressive tumor microenvironment, and optimal delivery methods is crucial to improve efficacy. Further investigations are required to gain a better understanding of natural killer cell-mediated responses, refine genetic engineering approaches, identify predictive biomarkers, and optimize combination strategies. Continued research and clinical trials will play a vital role in optimizing cell therapy and expanding treatment options for lymphoma patients.
Roshandel et al. (2026) studied this question.