Treg depletion has been reported previously as a primary mechanism driving the anti-tumor activity of systemic OX40 antibody immunotherapy [27], but this is the first report of a local effect of Treg depletion and reduced Treg-associated gene expression with the combination of SBRT, OX40 agonistic antibody, and TLR3/9 agonists in naturally occurring tumors. The gene discussed is TLR3; the disease is neoplasm.