CD4 and cancer: On the basis of these ideas, strategies that bypass the requirement of CD4+ T-cell-mediated help and compensate for apparently ‘helpless CD8+ T cells', such as treatment with agonistic anti-CD40L Ab (plus TNF-α blockade)16, or anti-PD-1 Ab50 may be the potential approaches to restore the ineffective cancer immunosurveillance in aged animals without distraction of defective CD4+ T cells.