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Vascular adhesion protein-1 (VAP-1) is an endothelial, cell surface–expressed oxidase involved in leukocyte traffic. The adhesive function of VAP-1 can be blocked by anti–VAP-1 Abs and small-molecule inhibitors. However, the effects of VAP-1 blockade on antitumor immunity and tumor progression are unknown. In this paper, we used anti–VAP-1 mAbs and small-molecule inhibitors of VAP-1 in B16 melanoma and EL-4 lymphoma tumor models in C57BL/6 mice. Leukocyte accumulation into tumors and neoangiogenesis were evaluated by immunohistochemistry, flow cytometry, and intravital videomicroscopy. We found that both anti–VAP-1 Abs and VAP-1 inhibitors reduced the number of leukocytes in the tumors, but they targeted partially different leukocyte subpopulations. Anti–VAP-1 Abs selectively inhibited infiltration of CD8-positive lymphocytes into tumors and had no effect on accumulation of myeloid cells into tumors. In contrast, the VAP-1 inhibitors significantly reduced only the number of proangiogenic Gr-1+CD11b+ myeloid cells in melanomas and lymphomas. Blocking of VAP-1 by either means left tumor homing of regulatory T cells and type 2 immune-suppressing monocytes/macrophages intact. Notably, VAP-1 inhibitors, but not anti–VAP-1 Abs, retarded the growth of melanomas and lymphomas and reduced tumor neoangiogenesis. The VAP-1 inhibitors also reduced the binding of Gr-1+ myeloid cells to the tumor vasculature. We conclude that tumors use the catalytic activity of VAP-1 to recruit myeloid cells into tumors and to support tumor progression. Small-molecule VAP-1 inhibitors therefore might be a potential new tool for immunotherapy of tumors.

We have read with interest the recent paper by Rothbard et al. ([1][1]), who suggest that small heat shock proteins (HSPs), including α B-crystallin, bind to human Abs as molecular chaperones rather than being recognized as an Ag. The authors state that this has led to the incorrect assignment of

In their recent paper, van den Brandt et al. ([1][1]) conclude that diabetes development in diabetes-prone BioBreeding (DP-BB) rats is due to an imbalance between Th17 effector (Th17eff) and regulatory T cells (Tregs) in favor of the Th17eff cells. DP-BB Treg function by itself was not hampered

Infections of cats with feline peritonitis (FIP) virus are usually inapparent but may lead to fatal polyserositis. We have recently advanced the hypothesis that immune complexes play an essential role in the pathogenesis of the condition. To support this hypothesis, the role of the third component of complement in FIP was investigated. In the present paper, the isolation of C3 from normal cat serum and some of its physical and immunologic properties are described. The final protein had an apparent m.w. of 185,000 and was composed of 2 polypeptide chains with m.w. of 128,000 and 71,000, respectively. When tested against whole cat serum, an antiserum raised in rabbits against purified C3 recognized only 1 protein whose identity with C3 was established. With the aid of this antiserum, depositions of C3 in renal glomeruli of FIP-affected cats were demonstrated by immunofluorescence. Their localizaton coincided with that of deposited IgG, thereby supporting the concept of an immune complex pathogenesis of FIP.