In contrast, FAP-expressing fibroblasts did not increase the invasiveness of the adenoma cell line. Conditioned medium from FAP-expressing fibroblasts increased the invasion in colon cancer cells, indicating an involvement Kinase Inhibitor Library mouse of mechanisms other than the protease activity of membrane-bound FAP. Further cell culture analysis showed that FGF1-expression is increased in FAP-expressing

fibroblasts. Conclusions: We demonstrate a novel function for FAP-expressing fibroblasts. Our findings also suggest that FAP may be a potential diagnostic marker for early invasion in colorectal cancer. Poster No. 150 CCL1 is a Novel Therapeutic Target for the Modulation of Treg Function with Implications for Cancer Immunotherapy Dominique B. Hoelzinger 1 , Shannon E. Smith1, Noweeda Mirza1, Ana Lucia Dominguez1, Soraya Zorro-Manrique1, Joseph Lustgarten1 1 Departmen of Immunology, Mayo College of Medicine, Scottsdale, AZ, USA The genetic instability of tumors Z-IETD-FMK mouse ensures a changing

landscape of mutated or over-expressed tumor associated antigens (TAAs). The presence of tumor-specific lymphocytes in tumors is evidence that TAAs are targets for T-cell immunity. In spite of this, established tumors rarely generate endogenous immunity leading to successful tumor eradication. A key reason for poor TAA immunity is that the tumor microenvironment becomes progressively more immunosuppressive as the tumor develops, inhibiting anti-tumor immune activity. The immunosuppressive milieu within tumors is largely brought about by the presence of T-regulatory cells (Tregs), which

maintain self-tolerance by directly inhibiting T-cells, NK cells and dendritic cells. Depletion of Tregs enhances antitumor immune responses, old however, it also affects the number of T-effector cells. Previous studies indicate that intratumoral injections of CpG-ODN strongly reduces the levels of Tregs within the tumor, and that the decrease in Tregs is mainly mediated by IL-6. Since IL6 promotes growth of some human cancers, alternate pathways to inactivate Tregs were sought through microarray analysis, resulting in gene candidates that can be exploited to modulate the function of Tregs. Chemokine (C-C motif) ligand 1 (CCL1) was expressed by Tregs and its neutralization both inhibited Treg conversion and suppressive function without affecting the function of T-effector cells. The combination of CpG-ODN and anti-CCL1 treatments induce complete rejection of tumors in BALB-neuT tolerant mice. Tumor rejection was coincident with changes in the lymphocyte composition in the tumor microenvironment. Tumors of CpG+anti-CCL1 treated mice have decreased in Treg numbers and a concomitant accumulation of tumorcidal cells within the tumor.