Send to

Choose Destination
See comment in PubMed Commons below
J Immunol. 2010 Apr 1;184(7):3442-9. doi: 10.4049/jimmunol.0904114. Epub 2010 Mar 1.

Blockade of programmed death ligand 1 enhances the therapeutic efficacy of combination immunotherapy against melanoma.

Author information

Department of Translational Science, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.


Inhibition of antitumor T cell responses can be mediated by the productive interaction between the programmed death-1 (PD-1) receptor on T cells and its ligand PD-L1. PD-L1 is highly expressed on both murine bone marrow-derived dendritic cells (DCs) and B16 melanoma. In this study, in vitro blockade of PD-L1 interaction on DCs led to enhanced IFN-gamma production and cytotoxicity by Ag-specific T cells. In vivo, the systemic administration of anti-PD-L1 Ab plus melanoma peptide-pulsed DCs resulted in a higher number of melanoma peptide-specific CD8(+) T cells, but this combination was insufficient to delay the growth of established B16 melanoma. Although the addition of 600 rad of total body irradiation delayed tumor growth, further adoptive transfer of Ag-specific CD8(+) T cells was needed to achieve tumor regression and long-term survival of the treated mice. Lymphopenic mice treated with anti-PD-L1 Ab demonstrated increased activation and persistence of adoptively transferred T cells, including a higher number of CD8(+) T cells infiltrating the tumor mass. Together, these studies support the blocking of PD-L1 signaling as a means to enhance combined immunotherapy approaches against melanoma.

[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center