Conclusions: Tumor-localizing NKp30/ICOSL vIgDs confer potent T cell costimulation via CD28 and ICOS dependent upon the tumor antigen B7-H6 and elicit encouraging efficacy against B7-H6+ tumors in vivo, including in combination with PD-1 inhibitors. The gene discussed is NCR3LG1; the disease is neoplasm.