TGFβ blockade in pancreatic cancer enhances sensitivity to combination chemotherapy

We evaluated the TGFβ blocking antibody NIS793 in combination with either gemcitabine/n(ab)-paclitaxel or FOLFIRINOX chemotherapy in orthotopic pancreatic cancer. Blockade of TGFβ with chemotherapy reduced tumor burden in poorly immunogenic pancreatic cancer, without affecting the metastatic rate of cancer cells. TGFβ blockade decreased total aSMA+ fibroblasts but had minimal effect on fibroblast heterogeneity. 6694c2 tumor cells were inoculated orthotopically into C57BL/6 mice treated with αTGFβ or Isotype, +/- GnP or FOLFIRINOX (5mg/kg oxaliplatin, 75mg/kg leucovorin, 50mg/kg irinotecan, and 75mg/kg 5-FU; dosed by i.v. at day 3 and day 6). Tumors were harvested on day 14, digested, and enriched for fibroblasts using antibodies against CD31 and CD90, followed by positive selection with magnetic beads and single cell transcriptional analysis. n = 5 tumors pooled per group.