CELL INTELLIGENCE · 肿瘤细胞治疗研究

Extranodal natural killer (NK)/T-cell lymphoma (ENKTCL) is one of the most aggressive non-Hodgkin lymphomas characterized by NK-cell or T-cell origins, a geographic prevalence in Asian and South American populations, and Epstein-Barr virus (EBV) infection. ENKTCL used to be a fatal disease upon treatment with anthracycline-containing chemotherapies. However, the treatment paradigms for ENKTCL have evolved; consequently, patients have achieved significantly improved clinical outcomes. Today, combined-modality therapies co-targeting genomic instability and metabolic vulnerability comprise the standard of care for early stage ENKTCL, whereas therapies that include targeting of immune and metabolic dysregulation are the backbone of treatment for advanced-stage ENKTCL. New agents targeting surface antigens, oncogenic signaling pathways, and EBV are under investigation and have demonstrated promising responses. Hematopoietic stem cell transplantation is beneficial when used in therapy-responsive, high-risk patients and ENKTCL-associated hemophagocytic lymphohistiocytosis, but it is not recommended for early stage ENKTCL. Although nearly 80% of patients with newly diagnosed ENKTCL achieve long-term survival, treatment of relapsed/refractory ENKTCL is critical. Because it is now understood that EBV infection has a major role in disease progression, a deeper understanding of EBV-associated oncogenesis and alterations in the tumor microenvironment foster the development of novel therapeutic strategies, such as cellular therapies and vaccines targeting EBV. Future multicenter collaborations worldwide will be needed to further optimize mechanism-based treatment in the era of precision medicine, paving a curative pathway for this once fatal disease.