T Cell-Mediated Antitumor Immunity Cooperatively Induced By TGFβR1 Antagonism and Gemcitabine Counteracts Reformation of the Stromal Barrier in Pancreatic Cancer

• Published in: Molecular cancer therapeutics Vol. 20; no. 10; pp. 1926 - 1940
• Main Authors: Li, Dandan, Schaub, Nicholas, Guerin, Theresa M, Bapiro, Tashinga E, Richards, Frances M, Chen, Vicky, Talsania, Keyur, Kumar, Parimal, Gilbert, Debra J, Schlomer, Jerome J, Kim, Seong-Jin, Sorber, Rebecca, Teper, Yaroslav, Bautista, Wendy, Palena, Claudia, Ock, Chan-Young, Jodrell, Duncan I, Pate, Nathan, Mehta, Monika, Zhao, Yongmei, Kozlov, Serguei, Rudloff, Udo
• Format: Journal Article
• Language: English
• Published: United States 01.10.2021
• Subjects: Animals; Antimetabolites, Antineoplastic - pharmacology; Apoptosis; Carcinoma, Pancreatic Ductal - drug therapy; Carcinoma, Pancreatic Ductal - immunology; Carcinoma, Pancreatic Ductal - metabolism; Carcinoma, Pancreatic Ductal - pathology; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Proliferation; Combined Modality Therapy; Deoxycytidine - analogs & derivatives; Deoxycytidine - pharmacology; Gemcitabine; Humans; Mice; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - immunology; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Receptor, Transforming Growth Factor-beta Type I - antagonists & inhibitors; Stromal Cells - drug effects; Stromal Cells - immunology; Stromal Cells - metabolism; Tumor Cells, Cultured; Tumor Microenvironment; Xenograft Model Antitumor Assays

The desmoplastic stroma of pancreatic cancers forms a physical barrier that impedes intratumoral drug delivery. Attempts to modulate the desmoplastic stroma to increase delivery of administered chemotherapy have not shown positive clinical results thus far, and preclinical reports in which chemother...