Subverting the B7-H1/PD-1 pathway in advanced melanoma and kidney cancer

Lauren C. Harshman, Toni K. Choueiri, Charles Drake, F. Stephen Hodi

Research output: Contribution to journalArticlepeer-review


Ligands for inhibitory immune receptors on T cells may be constitutively expressed on tumor cells or host cells in tumor microenvironment as a consequence of adaptive immunity. Programmed death 1 (PD-1) is 1 such receptor on T cells, which functions as a negative regulator of T cell activity. Tumors that up-regulate programmed death ligand 1 (PD-L1) (B7-H1) may abrogate the host's effector T cell antitumor response. Higher tumoral PD-L1 expression has been linked with inferior clinical outcomes. Multiple cancers including renal cell cancers (RCCs) and melanomas have relatively high levels of PD-L1 on the cell surface. Early evaluations of antibodies that block the interaction of PD-1 and PD-L1 have shown efficacy and a favorable tolerability profile with notable inflammatory toxicities that are generally manageable. Upward of 30% of RCC patients and 50% of melanoma patients achieve objective responses. Durable responses can occur, even in some patients who have discontinued treatment. The developing investigation of PD-1/PD-L1 pathway-blocking agents in RCC and melanoma will likely alter our approaches to the treatment of these 2 deadly diseases.

Original languageEnglish (US)
Pages (from-to)272-280
Number of pages9
JournalCancer Journal (United States)
Issue number4
StatePublished - 2014


  • antibody
  • kidney cancer
  • melanoma
  • MK-3475
  • MPDL3280A
  • nivolumab
  • PD-1
  • PD-L1
  • renal cell carcinoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)


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