Recently, a joint physician-scientist team led by Professor Ting Liu and Professor Yu Liu from Department of Hematology, West China Hospital and State Key Laboratory of Biotherapy, Sichuan University, reported in Blood that they had developed a novel immunotherapy for Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH), a life-threatening virus-related blood disease.

EBV-HLH is a fatal hyperinflammatory syndrome characterized by uncontrolled activation of immune cells, and triggered by EBV infection. Currently, it is treated with chemotherapies to remove hyperactive immune cells. Unfortunately, chemotherapies cannot eliminate the virus, the initiator of the disease. Therefore, EBV-HLH invariably becomes relapsed or refractory. Professors Liu and Liu found that a new immunotherapy with nivolumab only could lead to complete remission in 5 out of 7 EBV-HLH patients. More strikingly, this new treatment completely eradicated EBV infection. Nivolumab is an antibody against a gene named programmed cell death 1 (PD-1) and has been successfully applied in treating cancer patients. Paradoxically, it is generally believed to enhance the functions of immune cells, mostly the T cells. Thus, it seems at odds with its application for this hyperinflammatory syndrome. Liu and Liu team decided to decipher the mystery by analyzing the gene activities of the whole genome in each immune cell with a cutting-edge technique, single cell RNA-sequencing. They found that, surprisingly, the long-believed hyperactive immune cells in EBV-HLH patients were actually immune defective. And nivolumab normalized the patients’ immune system and enhanced its capacity for virus clearance. Consequently, this study has discovered a cure for this otherwise incurable disease and illustrated an unprecedent molecular mechanism.

This study was published in the March 12 issue of Blood, a top journal in hematology, with the title Nivolumab treatment of relapsed/refractory Epstein-Barrvirus–associated hemophagocytic lymphohistiocytosis in adults. In their commentary paperCheckmate for EBV-HLH, Professor Kenneth L. McClain and Professor Nader Kim El-Mallawany in Baylor College of Medicine, two experts in HLH, thought that “the work of Liu et al presents exciting preliminary data” on immunotherapies for EBV-HLH and is a “checkmate” for this disease. Dr. Pengpeng Liu, a post-doctoral fellow at West China Hospital, and Xiangyu Pan, a graduate student of State Key Laboratory of Biotherapy and graduate from the 1st Innovation class of SKLB are the two first authors. Ting Liu and Yu Liu are the corresponding authors. Other authors include Drs. Ting Niu, Xiao Shuai, Jiazhuo Liu, Yong Guo, Liping Xie and Yu Wu in Department of Hematology, West China Hospital and Prof. Chong Chen, Jian Wang and Xuelan Chen in State Key laboratory of Biotherapy.

More information about this study can be found at Blood podcast (https://ashpublications.org/blood/pages/blood_podcast).