The anticancer immune response of anti-PD-1/PD-L1 and the genetic determinants of response to anti-PD-1/PD-L1 antibodies in cancer patients

// Xinbing Sui 1,2,3,* , Junhong Ma 5,* , Weidong Han 1,2 , Xian Wang 1,2 , Yong Fang 1,2 , Da Li 1 , Hongming Pan 1,2,3 and Li Zhang 3,4 1 Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China 2 Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China 3 Department of Immunology, University of Toronto, Toronto, ON, Canada 4 Transplantation Institute and Toronto General Research Institute, University Health Network, Toronto, Canada 5 Department of Gastrointestinal Surgery, Nankai Hospital, Nankai District, Tianjin, China * These authors have contributed equally to this work Correspondence to: Hongming Pan, email: // Li Zhang, email: // Keywords : PD-1, PD-L1, cancer, checkpoint inhibitor, immunotherapy Received : May 26, 2015 Accepted : July 08, 2015 Published : August 05, 2015 Abstract The programmed death-1 (PD-1), a coinhibitory receptor expressed on activated T cells and B cells, is demonstrated to induce an immune-mediated response and play a critical role in tumor initiation and development. The cancer patients harboring PD-1 or PD ligand 1 (PD-L1) protein expression have often a poor prognosis and clinical outcome. Currently, targeting PD-1 pathway as a potential new anticancer strategy is attracting more and more attention in cancer treatment. Several monoclonal antibodies against PD-1 or PD-L1 have been reported to enhance anticancer immune responses and induce tumor cell death. Nonetheless, the precise molecular mechanisms by which PD-1 affects various cancers remain elusive. Moreover, this therapy is not effective for all the cancer patients and only a fraction of patients respond to the antibodies targeting PD-1 or PD-L1, indicating these antibodies may only works in a subset of certain cancers. Thus, understanding the novel function of PD-1 and genetic determinants of response to anti-PD-1 therapy will allow us to develop a more effective and individualized immunotherapeutic strategy for cancer.