Oncolytic HSV1716 attenuates tumor-killing activity of infected primary NK cells

Area of Science:

• Immunology
• Virology
• Oncology

Background:

• Oncolytic herpes simplex virus type-1 (HSV1)-based therapies leverage innate immunity, particularly natural killer (NK) cells, for cancer treatment.
• NK cells are crucial antiviral effector cells that eliminate virus-infected tumor cells.

Purpose of the Study:

• To investigate the interaction between the oncolytic HSV1 variant, HSV1716, and primary human NK cells.
• To understand how HSV1716 infection affects NK cell function and phenotype.

Main Methods:

• Co-culture experiments of HSV1716-infected tumor cells with primary human NK cells.
• Analysis of NK cell activation, degranulation, and viral gene expression.
• Single-cell sequencing to assess gene expression changes in infected NK cells.

Main Results:

• HSV1716-infected tumor cells induced NK cell activation and degranulation, despite reduced activating ligand expression.
• Primary human NK cells were infected by HSV1716 upon co-culture with infected tumor cells, showing viral gene expression and increased viral load.
• HSV1716 infection led to downregulation of key NK effector genes and altered stress-response pathways, resulting in diminished NK cell cytotoxic capacity.

Conclusions:

• Primary human NK cells can be infected by HSV1716, leading to functional impairment and reduced tumor cell killing.
• These findings have implications for optimizing oncolytic virus therapy strategies, particularly concerning NK cell involvement and treatment timing.