Single-cell analysis of oncolytic virotherapy in adult T-cell leukemia/lymphoma.

Abstract

Adult T-cell leukemia/lymphoma (ATLL), an aggressive T-cell malignancy associated with human T-cell leukemia virus type 1, presents significant therapeutic challenges due to high relapse rates and resistance to therapy. Here, we present the first reported case of ATLL treated with talimogene laherparepvec (T-VEC), an oncolytic viral immunotherapy approved for unresectable melanoma. The patient, who had experienced disease progression despite multiple lines of chemotherapy, radiotherapy, immunotherapy, and targeted therapy, underwent experimental virotherapy with two intratumoral T-VEC injections. The treatment was well-tolerated, with no significant adverse effects, and led to substantial tumor regression and clinical stabilization, suggesting potential remission. Single-cell analysis revealed that T-VEC treatment induced robust local and systemic immune responses, including tumor necrosis, activation of M1 macrophages, and infiltration of CD8+ effector memory T cells. These findings demonstrate T-VEC's safety and efficacy in generating both localized oncolysis and systemic anti-tumor immune response, highlighting its promise as a novel therapeutic approach for refractory ATLL.