PD-1 is a regulator of NY-ESO-1-specific CD8+ T cell expansion in melanoma patients.

This just came out!!!!!!!!!!

Dear James Breitfeller!

"Hot off the press - below is a roundup of recent papers
which have been authored by you, by one of your co-authors,
or from scientists in your contacts or bookmarks." Well I know I did not write this, so I must have been Dr. Kirkwood and Colleages


Fourcade Julien; Kudela Pavol; Sun Zhaojun; Shen Hongmei; Land Stephanie R; Lenzner Diana; Guillaume Philippe; Luescher Immanuel F; Sander Cindy; Ferrone Soldano; Kirkwood John M; Zarour Hassane M

Journal of immunology (Baltimore, Md. : 1950) 2009;182(9):5240-9

Department of Medicine and Division of Hematology/Oncology, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15213, USA.

"The programmed death 1 (PD-1) receptor is a negative regulator of activated T cells and is up-regulated on exhausted virus-specific CD8(+) T cells in chronically infected mice and humans. Programmed death ligand 1 (PD-L1) is expressed by multiple tumors, and its interaction with PD-1 resulted in tumor escape in experimental models. To investigate the role of PD-1 in impairing spontaneous tumor Ag-specific CD8(+) T cells in melanoma patients, we have examined the effect of PD-1 expression on ex vivo detectable CD8(+) T cells specific to the tumor Ag NY-ESO-1. In contrast to EBV, influenza, or Melan-A/MART-1-specific CD8(+) T cells, NY-ESO-1-specific CD8(+) T cells up-regulated PD-1 expression. PD-1 up-regulation on spontaneous NY-ESO-1-specific CD8(+) T cells occurs along with T cell activation and is not directly associated with an inability to produce cytokines.

Importantly, blockade of the PD-1/PD-L1 pathway in combination with prolonged Ag stimulation with PD-L1(+) APCs or melanoma cells augmented the number of cytokine-producing, proliferating, and total NY-ESO-1-specific CD8(+) T cells. Collectively, our findings support the role of PD-1 as a regulator of NY-ESO-1-specific CD8(+) T cell expansion in the context of chronic Ag stimulation. They further support the use of PD-1/PD-L1 pathway blockade in cancer patients to partially restore NY-ESO-1-specific CD8(+) T cell numbers and functions, increasing the likelihood of tumor regression. "


What does it mean?????

Programmed death-1 blockade (anti-PD-1 mAb) enhances expansion and functional capacity of human melanoma antigen-specific CTLs.

"The increased frequencies and absolute numbers of antigen-specific CTLs by PD-1 blockade resulted from augmented proliferation, not decreased apoptosis. Kinetic analysis of cytokine secretion demonstrated that PD-1 blockade increased both type-1 and type-2 cytokine accumulation in culture without any apparent skewing of the cytokine repertoire."

These findings have implications for developing new cancer immunotherapy strategies for Melanoma!!!!!!!

I believe Yale and MD Anderson have trials with the Moffit Center in Flordia coming on soon.

Jimmy B