Costimulatory b7-h1 in renal cell carcinoma patients: indicator of tumor aggressiveness and potential therapeutic target

Abstract

The invention features methods of diagnosis by assessing B7-H1 expression in a tissue from a subject that has, or is suspected of having, cancer, methods of treatment with agents that interfere with B7-H1-receptor interaction, methods of selecting candidate subjects likely to benefit from cancer immunotherapy, and methods of inhibiting expression of B7-H1.

What is claimed is: 
     
         1 . A method for the immunotherapy treatment of a subject with cancer, comprising:
 (a) identifying whether the subject is suitable for immunotherapy, the identifying comprising providing a tissue sample from the subject, which contains test cells, wherein the test cells comprise tumor cells and/or tumor-infiltrating leukocytes, and assessing the proportion of test cells in the tissue sample that express B7-H1, the identification being made if <10% of the tumor cells express B7-H1 and/or if an adjusted expression score of the tumor-infiltrating leukocytes is <100; and   (b) administering an agent for immunotherapy to the subject,   
       wherein said cancer is renal cell carcinoma. 
     
     
         2 . The method of  claim 1 , wherein the subject is a human. 
     
     
         3 . The method of  claim 1 , wherein the immunotherapy treatment is a passive immunotherapy treatment. 
     
     
         4 . The method of  claim 1 , wherein the immunotherapy treatment is an active immunotherapy treatment. 
     
     
         5 . The method of  claim 1 , wherein said agent for immunotherapy is at least one agent selected from the group consisting of interleukin-2, interleukin-4, interleukin-10, interleukin-12, interleukin-13, interferon-gamma, an antibody specific to interferon-gamma, an antibody specific to interleukin-1, an antibody specific to interleukin-4, an antibody specific to interleukin-6, an antibody specific to interleukin-8, an antibody specific to interleukin-10, an antibody specific to interleukin-12, an antibody specific to interleukin-13, an antibody specific to tumor necrosis factor-alpha, an antibody specific to macrophage inflammatory protein-1, an antibody specific to macrophage inflammatory protein-3alpha, an antibody specific to monocyte chemoattractant protein-1, an antibody specific to epithelial neutrophil activating peptide-78, an antibody specific to interferon-gamma-inducible protein-10, interferon-gamma, interferon-alpha, interferon-beta, tumor necrosis factor-alpha, granulocyte macrophage colony stimulating factor, T-cells, killer cells, B cells, and antigen-presenting cells. 
     
     
         6 . The method of  claim 1 , wherein said agent for immunotherapy is at least one agent selected from the group consisting of interleukin-2, interleukin-12, tumor necrosis factor-alpha, and T-cells. 
     
     
         7 . The method of  claim 1 , wherein said assessing comprises contacting said tissue sample with an antibody that specifically binds to B7-H1 polypeptide. 
     
     
         8 . The method of  claim 1 , wherein said immuno-inhibitory threshold level is determined by performing a statistical analysis of the correlation between the proportion of cancer cells and/or tumor-infiltrating leukocytes expressing B7-H1 in a group of subjects with said cancer and an expected risk of death in said group of subjects, and assigning a statistically significant cut-off value for said correlation. 
     
     
         9 . The method according to  claim 8 , wherein the statistical analysis is performed using a scatter plot.