Oncolytic herpes simplex virus type-1 (HSV1)–based therapies engage innate immune responses, including natural killer (NK) cells, which are regarded as antiviral effector cells that eliminate virus-infected tumor targets. In this study, we examined interactions between the HSV1–derived oncolytic virus HSV1716 and primary human NK cells. Co-culture experiments revealed increased activation and degranulation of NK cells in response to HSV1716-infected tumor cells, despite the downregulation of ligands for NK-cell activating receptors on infected targets. Following co-culture with infected tumor cells, but not after incubation with viral inoculum alone, viral gene expression and increased viral copy numbers were detected in NK cells, indicating enhanced viral acquisition and persistence associated with target-cell contact. HSV1716-infected NK cells displayed impaired tumor cell killing ability. Single-cell sequencing analysis revealed downregulation of key NK effector genes alongside alterations in stress-response pathways in HSV1716 infected NK cells. Together, these findings demonstrate that primary human NK cells are infected by HSV1716 and undergo functional and phenotypic changes, leading to a diminished cytotoxic capacity. Given the emerging role of NK cell–based therapies in cancer, these findings may be relevant for the design and timing of oncolytic virus–based strategies in the future.
K. Susek, D. Holla, C. Marsal et al.· Frontiers in Immunology· 0 citations
Adoptive immunotherapies have emerged as a promising strategy in the treatment of hematological malignancies. To date, seven chimeric antigen receptor (CAR)-T cell products have obtained market authorization in Europe for B-cell malignancies, where they have revolutionized treatment for eligible patients. In addition, natural killer (NK) cells and γδ T cells are of particular interest for cell-based therapies due to their strong intrinsic cytotoxicity and favorable safety profile. Addressing challenges facing the clinical translation of NK cell therapies was one of the issues discussed in the NK & ILC Symposium that took place in Freiburg, Germany from March 11 to 13, 2026, as the annual meeting of the NK & ILC study group of the German Society for Immunology (DGfI). Topics ranging from basic immunological research to technological innovations and clinical trial results were discussed during the 3-day conference, spanning over 40 presentations and 100 posters. A highlight of the conference was a workshop featuring short presentations and a panel discussion that focused specifically on the current challenges and future prospects of the clinical implementation of NK cell therapies; the findings of this workshop are summarized in this opinion paper. Graphical abstract
L. Knapp, Katharina Sophie Fischer, Janika Sosat et al.· Human Gene Therapy· 0 citations
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