GM-CSF-recruited MDSCs negate anti-tumor CD8+CTL re-
sponses in PDA and promote metastatic progression (Bayne
et al., 2012; Connolly et al., 2010; Pylayeva-Gupta et al., 2012).
Effector T cells are also thought to be excluded from the PDA
TME by CXCL12 produced by a subset of carcinoma-associated
fibroblasts which express fibroblast activation protein (FAP)Figure 5.gdT Cell Deletion Results in CD4+T Cell Th1 Differentiation, CD8+T Cell Activation, andabT Cell-Dependent Tumor Protection in
Invasive PDA
(A–D) WT and Tcrd–/–mice were orthotopically implanted with KPC-derived tumor cells. On day 21, tumor-infiltrating CD4+and CD8+T cells were interrogated for
(A) co-expression of TNF-aand IFN-g, (B) expression of T-bet, (C) GATA-3, and (D) FoxP3. Representative contour plots and quantitative data are shown.
Experiments were repeated twice with similar results (n = 5/group; p < 0.05).
(E) WT and Tcrd–/–pancreata were orthotopically implanted with KPC-derived tumor cells and serially treated witha-CD4 anda-CD8 neutralizing mAbs or isotype
controls. Pancreatic tumors were harvested at 3 weeks. Representative images and tumor weights are shown (n = 5/group; p < 0.05, **p < 0.01, ***p < 0.001).
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