Paired tumour infiltrating lymphocyte (TIL) and tumour cell line from bladder cancer: a new approach to study tumour immunology in vitro |
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Affiliation: | 1. Department of Medical Oncology, The Royal London Hospital, Whitechapel, London, E1 1BB UK;2. Department of Immunology, The Royal London Hospital, Whitechapel, London, E1 1BB UK;3. Department of Cytogenetics, Queen Elizabeth Hospital, London, U.K.;1. Division of Engineering in Medicine and Division of Renal Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115 USA;2. Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA;3. Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA;4. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA;1. Center for Vascular and Heart Research, Fralin Biomedical Research Institute, Virginia Tech, Roanoke, VA 24016, USA;2. Department of Pharmacology and Biochemistry, Faculty of Pharmacy, Horus University, New Damietta 34518, Egypt;3. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt;4. Cancer Biology Department, Pharmacology Unit, National Cancer Institute (NCI), Cairo University, Cairo, Egypt;5. Department of Chemistry of Natural and Microbial Products, Division of Pharmaceutical and Drug Industries, National Research Centre, Cairo, Egypt;6. Department of Neurology, Faculty of Physical Therapy, Horus University, New Damietta 34518, Egypt;7. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian University, 6th of October City, Giza 12566, Egypt;8. Chemical and Biological Integrative Research Center, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea;9. Division of Bio-Medical Science & Technology, University of Science and Technology, Daejeon 34113, Republic of Korea;10. BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, Goyang 10326, Republic of Korea;11. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt;12. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Horus University-Egypt, New Damietta 34518, Egypt;1. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA;2. Department of Pathology, Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA;3. Department of Immunology, Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA;1. CEA, Institute of Emerging Diseases and Innovative Therapies (iMETI), Research Division in Hematology and Immunology (SRHI), Saint-Louis Hospital, Paris, France;2. University Paris Diderot, Sorbonne Paris Cité, UMR E_5 Institut Universitaire d’Hematologie, Saint-Louis Hospital, Paris, France;3. Urology Department, Saint-Louis Hospital, Paris, France;1. Centre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, Queensland, 4059, Australia;2. Cancer Precision Medicine Group, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Queensland, 4006, Australia;3. Faculty of Health, Queensland University of Technology, Brisbane, Queensland, 4059, Australia;4. Faculty of Medicine, The University of Queensland, Queensland, 4072, Australia;5. Proteomics and Metabolomics Platform, La Trobe University, Melbourne, VIC, 3083, Australia;1. Department of Pediatrics, St. Louis Children’s Hospital, St. Louis, Missouri;2. Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, Missouri;3. Diabetes Clinical Research Program and Center for Interventional Immunology, Benaroya Research Institute at Virginia Mason, Seattle, Washington;4. Department of Medicine, Diabetes Center, University of California, San Francisco, California;5. Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, California;6. Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, Washington |
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Abstract: | This paper reports the first example of tumour infiltrating lymphocytes (TILs) and a tumour cell line from the same individual and analyses their characteristics. The tumour cell line (CAT), derived from a patient with well-differentiated (G3pTa) TCC, has been in culture for 24 months and subcultured more than 100 times. Epithelial origin was established by electronmicroscopy and use of a range of monoclonal antibodies (Mabs) against cytokeratins. The TILs isolated from the same tumour expressed all the phenotypic characteristics of normal activated T cells and demonstrated low levels of cytotoxicity against the autologous tumour line (CAT). Comparison of cell surface molecules of these cells revealed the loss of HLA-B7, B44 and Bw6 from the CAT cells whilst maintaining HLA-A2, A3 and Bw4. Karyotypic analysis demonstrated three rearranged chromosomes (between chromosomes 4 and 11, 10 and 13, 11 and 17) on CAT cells. The potential that study of paired autologous tumour cells and TILs in culture offers for studying the role of MHC antigens in tumour rejection and the impact of different approaches to correcting the defect are reviewed. |
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