Human cancer immunotherapy with antibodies to the PD-1 and PD-L1 pathway

Kim C. Ohaegbulam, Amer Assal, Eszter Lazar-Molnar, Yu Yao, Xingxing Zang

Research output: Contribution to journalReview article

243 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)24-33
Number of pages10
JournalTrends in Molecular Medicine
Volume21
Issue number1
DOIs
StatePublished - Jan 1 2015

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Keywords

  • Human cancer
  • Immunotherapy
  • Monoclonal antibody
  • PD-1
  • PD-L1
  • PD-L2

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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