The hypothesis behind designing this innovative triple agent combination was that restoration of the multifactorial tumor suppressor gene TUSC2, deficient in 80% of NSCLC, will modulate the tumor immune microenvironment by changing its context from an immunosuppressive to immunostimulatory milieu, which will prime tumors for better response to chemo–immunotherapy. The gene discussed is TUSC2; the disease is neoplasm.