title: Dendritic cells loaded with pancreatic Cancer Stem Cells (CSCs) lysates induce antitumor immune killing effect in vitro.
abstract: According to the cancer stem cells (CSCs) theory, malignant tumors may be heterogeneous in which a small population of CSCs drive the progression of cancer. Because of their intrinsic abilities, CSCs may survive a variety of treatments and then lead to therapeutic resistance and cancer recurrence. Pancreatic CSCs have been reported to be responsible for the malignant behaviors of pancreatic cancer, including suppression of immune protection. Thus, development of immune strategies to eradicate pancreatic CSCs may be of great value for the treatment of pancreatic cancer. In this study, we enriched pancreatic CSCs by culturing Panc-1 cells under sphere-forming conditions. Panc-1 CSCs expressed low levels of HLA-ABC and CD86, as measured by flow cytometry analysis. We further found that the Panc-1 CSCs modulate immunity by inhibiting lymphocyte proliferation which is promoted by phytohemagglutinin (PHA) and anti-CD3 monoclonal antibodies. The monocyte derived dendritic cells (DCs) were charged with total lysates generated from Panc-1 CSCs obtained from tumor sphere culturing. After co-culturing with lymphocytes at different ratios, the Panc-1 CSCs lysates modified DC effectively promoted lymphocyte proliferation. The activating efficiency reached 72.4% and 74.7% at the ratios of 1∶10 and 1∶20 with lymphocytes. The activated lymphocytes secreted high levels of INF-γ and IL-2, which are strong antitumor cytokines. Moreover, Panc-1 CSCs lysates modified DC induced significant cytotoxic effects of lymphocytes on Panc-1 CSCs and parental Panc-1 cells, respectively, as shown by lactate dehydrogenase (LDH) assay. Our study demonstrates that the development of CSCs-based vaccine is a promising strategy for treating pancreatic cancer.
authors.affiliation: Pancreatic Disease Institute, Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei, P. R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yin
authors.affiliation: Pancreatic Disease Institute, Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei, P. R. China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Shi
authors.affiliation: Pancreatic Disease Institute, Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei, P. R. China.
authors.forename: Shanmiao
authors.initials: S
authors.lastname: Gou
authors.affiliation: Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Shen
authors.affiliation: Pancreatic Disease Institute, Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei, P. R. China.
authors.forename: Chunyou
authors.initials: C
authors.lastname: Wang
mesh_terms: D051940:B7-2 Antigen / Q000235:genetics / Q000378:metabolism; D002457:Cell Extracts / Q000494:pharmacology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology; D014411:Neoplastic Stem Cells / Q000737:chemistry / Q000276:immunology*; D010190:Pancreatic Neoplasms / Q000276:immunology*
chemical_list: D051940:B7-2 Antigen; D002457:Cell Extracts; D006680:HLA Antigens; D007376:Interleukin-2; D007371:Interferon-gamma