Pancreatic ductal adenocarcinoma (PDA) is a particularly deadly form of cancer for which few therapies have shown efficacy. The tumor microenvironment in PDA is largely immunosuppressive, blocking antitumor immunity. Beatty et al. treated a small cohort of PDA patients with gemcitabine chemotherapy plus a monoclonal antibody that activates CD40, a protein known to promote T cell immunity. Because this combination showed efficacy in a small number of patients, the same treatment was analyzed in a mouse model of PDA. A subset of CD40 antibody–treated mice also showed tumor regressions. However, the antitumor effects depended not on T cells but on macrophages. Macrophages that had infiltrated the tumors after antibody treatment were also tumoricidal in vitro. Thus, activation of macrophages by CD40 may promote antitumor immunity in PDA.
G. L. Beatty, E. G. Chiorean, M. P. Fishman, B. Saboury, U. R. Teitelbaum, W. Sun, R. D. Huhn, W. Song, D. Li, L. L. Sharp, D. A. Torigian, P. J. O’Dwyer, R. H. Vonderheide, CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science 331, 1612–1616 (2011). [Abstract] [Full Text]