The study investigates the role of B7-H1, a B7 family molecule, in the resistance of tumors to therapeutic anti-CD137 antibody treatment. The authors found that constitutive or inducible expression of B7-H1 on mouse tumors confers resistance to anti-CD137 antibody therapy, leading to failure of antigen-specific CD8+ CTLs to destroy tumor cells. Blockade of B7-H1 or PD-1, a receptor for B7-H1, by specific monoclonal antibodies reversed this resistance and enhanced therapeutic efficacy. The findings suggest that B7-H1/PD-1 forms a molecular shield that prevents CTLs from lysing tumor cells, and implicate B7-H1/PD-1 blockade as a potential strategy to enhance cancer immunotherapy.The study investigates the role of B7-H1, a B7 family molecule, in the resistance of tumors to therapeutic anti-CD137 antibody treatment. The authors found that constitutive or inducible expression of B7-H1 on mouse tumors confers resistance to anti-CD137 antibody therapy, leading to failure of antigen-specific CD8+ CTLs to destroy tumor cells. Blockade of B7-H1 or PD-1, a receptor for B7-H1, by specific monoclonal antibodies reversed this resistance and enhanced therapeutic efficacy. The findings suggest that B7-H1/PD-1 forms a molecular shield that prevents CTLs from lysing tumor cells, and implicate B7-H1/PD-1 blockade as a potential strategy to enhance cancer immunotherapy.