The use of a murine model of anti-PD-1–refractory mammary cancer was used to study the combination of anti-OX40 with anti-PD-1 and demonstrated that concomitant use anti-PD-1 antibody attenuated the therapeutic effects of anti-OX40 including increases in exhaustion markers and significantly reduce CD4+ and CD8+ T-cell proliferation compared to untreated mice. The gene discussed is CD4; the disease is breast cancer.