Abstract
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 language | English (US) |
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Pages (from-to) | 272-280 |
Number of pages | 9 |
Journal | Cancer Journal (United States) |
Volume | 20 |
Issue number | 4 |
DOIs | |
State | Published - 2014 |
Keywords
- antibody
- kidney cancer
- melanoma
- MK-3475
- MPDL3280A
- nivolumab
- PD-1
- PD-L1
- renal cell carcinoma
ASJC Scopus subject areas
- Cancer Research
- Oncology
- General Medicine