Activity and Immune Correlates of a Programmed Death-1 Blockade Antibody in the treatment of Refractory Solid Tumors

Background: Blockade of programmed death 1 (PD-1), an inhibitory T lymphocyte receptor, is associated with immune system enhancement and tumor remission in various tumors. We assessed the anti-tumor activity and immune correlates of cancer patients treated with an anti-PD-1 antibody. Patients and Methods: Twelve patients with advanced metastatic tumors were treated with anti-PD-1 antibody. Responses were assessed after a 12-week treatment regimen. Biochemical and immunological indexes were measured before each cycle. Results: Among the 12 patients, 3 patients showed partial response while 6 patients had stable disease (objective response rate: 3/12, 25%; disease control rate: 9/12, 75%). During immunotherapy, the proportion of circulating CD3⁺ T lymphocytes remained stable, with decreasing trends of CD3⁺CD4⁺ T helper cell and increase in CD3⁺CD8⁺ T memory cells, in patients with stable disease. Additionally, an increase in serum lactate dehydrogenase levels seemed to correlate with tumor progression. Conclusions: An anti-PD-1 antibody produced objective responses in approximately 25% patients with various solid tumors, demonstrating that it could improve the immune system in vivo.