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.
Highlights
programmed death-1 (PD-1) expression by tumor-infiltrating lymphocytes www.impactjournals.com/oncotarget (TILs) was proved to correlate with impaired immune responses and poor outcome in several tumor types [12, 13]
PD-1 is expressed on peripheral T cells, B cells, natural killer T (NKT) cells, dendritic cells (DCs) and some monocytes upon their activation [24]
Blockade of PD-1 increased the activation of phosphatidylinositol-3-kinase (PI3K) and its downstream targets AKT and mammalian target of rapamycin, which are impaired in antiviral cytotoxic T lymphocytes (CTLs)
Summary
PD-1 expression by tumor-infiltrating lymphocytes www.impactjournals.com/oncotarget (TILs) was proved to correlate with impaired immune responses and poor outcome in several tumor types [12, 13]. Based on the concept that the blockade of PD-1 or its ligands has immune-potentiating effects on cancer cells, many monoclonal antibodies targeting PD-1/PD-L1 pathway have been developed for the treatment of various cancer types (Table 1). These data support that nivolumab has antitumor activity and a manageable safety profile in previously treated patients with advanced, refractory, squamous NSCLC.
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