TY - JOUR
T1 - Human cancer immunotherapy with antibodies to the PD-1 and PD-L1 pathway
AU - Ohaegbulam, Kim C.
AU - Assal, Amer
AU - Lazar-Molnar, Eszter
AU - Yao, Yu
AU - Zang, Xingxing
N1 - Publisher Copyright:
© 2014 Elsevier Ltd.
PY - 2015
Y1 - 2015
N2 - The programmed death 1 (PD-1) receptor and its ligands programmed death ligand 1 (PD-L1) and PD-L2, members of the CD28 and B7 families, play critical roles in T cell coinhibition and exhaustion. Overexpression of PD-L1 and PD-1 on tumor cells and tumor-infiltrating lymphocytes, respectively, correlates with poor disease outcome in some human cancers. Monoclonal antibodies (mAbs) blockading the PD-1/PD-L1 pathway have been developed for cancer immunotherapy via enhancing T cell functions. Clinical trials with mAbs to PD-1 and PD-L1 have shown impressive response rates in patients, particularly for melanoma, non-small-cell lung cancer (NSCLC), renal cell carcinoma (RCC), and bladder cancer. Further studies are needed to dissect the mechanisms of variable response rate, to identify biomarkers for clinical response, to develop small-molecule inhibitors, and to combine these treatments with other therapies.
AB - The programmed death 1 (PD-1) receptor and its ligands programmed death ligand 1 (PD-L1) and PD-L2, members of the CD28 and B7 families, play critical roles in T cell coinhibition and exhaustion. Overexpression of PD-L1 and PD-1 on tumor cells and tumor-infiltrating lymphocytes, respectively, correlates with poor disease outcome in some human cancers. Monoclonal antibodies (mAbs) blockading the PD-1/PD-L1 pathway have been developed for cancer immunotherapy via enhancing T cell functions. Clinical trials with mAbs to PD-1 and PD-L1 have shown impressive response rates in patients, particularly for melanoma, non-small-cell lung cancer (NSCLC), renal cell carcinoma (RCC), and bladder cancer. Further studies are needed to dissect the mechanisms of variable response rate, to identify biomarkers for clinical response, to develop small-molecule inhibitors, and to combine these treatments with other therapies.
KW - Human cancer
KW - Immunotherapy
KW - Monoclonal antibody
KW - PD-1
KW - PD-L1
KW - PD-L2
UR - http://www.scopus.com/inward/record.url?scp=84925529257&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84925529257&partnerID=8YFLogxK
U2 - 10.1016/j.molmed.2014.10.009
DO - 10.1016/j.molmed.2014.10.009
M3 - Review article
C2 - 25440090
AN - SCOPUS:84925529257
SN - 1471-4914
VL - 21
SP - 24
EP - 33
JO - Trends in Molecular Medicine
JF - Trends in Molecular Medicine
IS - 1
ER -