Novel inhibitory and co-stimulatory immune checkpoints such as lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin mucin-3 (TIM-3), T cell immunoreceptor with Ig and ITIM domains (TIGIT), OX40, CD137 (4-1BB), and CD40 are examined for their potential to enhance anti-tumor immunity. The gene discussed is TNFRSF4; the disease is neoplasm.