title: Expansion of anti-mesothelin specific CD4+ and CD8+ T cell responses in patients with pancreatic carcinoma.
abstract: We aimed to assess the status of naturally occurring CD4(+) and CD8(+) T cell responses to a tumour associated antigen, Mesothelin, in patients with pancreatic carcinoma and study the effects of elevated IL-10 on Mesothelin-specific T cell responses. For that sake, short term T cell lines were generated from PBMCs of 16 healthy controls, 15 patients with benign pancreatic diseases and 25 patients with pancreatic carcinoma and Mesothelin-specific CD4(+) and CD8(+) T cell responses were analysed using intracellular cytokine assays for IFN-γ. Plasma levels of IL-10 and Mesothelin were measured using cytometric bead array and ELISA assay, respectively. The blocking assays were performed to assess the effects of IL-10 on Mesothelin-specific T cell responses. Here, we demonstrate that the plasma levels of Mesothelin and IL-10 are significantly increased in patients with pancreatic carcinoma. Additionally, we found that (a) Mesothelin-specific T cell responses are significantly expanded in cancer patients (p = 0.0053), (b) the multifunctional CD4(+) T cell response is directed toward a broad repertoire of epitopes within the Mesothelin protein. (c) Mesothelin-specific CD4+ T cell response is directly inhibited by elevated IL-10 in cancer patients. These data provides evidence for the use of Mesothelin as an immunogen for tumour-specific T cell response.
authors: The Institute for Liver and Digestive Health, University College London, London, United Kingdom ; Institute of Immunity and Transplantation, University College London and the Royal Free London NHS Foundation Trust, London, United Kingdom.
authors: Yuan
authors: Y
authors: Chen
authors: Department of Medicine, Imperial College London, London, United Kingdom.
authors: Lakshmana
authors: L
authors: Ayaru
authors: Department of Medicine, Imperial College London, London, United Kingdom.
authors: Sanju
authors: S
authors: Mathew
authors: Institute of Immunity and Transplantation, University College London and the Royal Free London NHS Foundation Trust, London, United Kingdom.
authors: Emma
authors: E
authors: Morris
authors: The Institute for Liver and Digestive Health, University College London, London, United Kingdom.
authors: Stephen P
authors: SP
authors: Pereira
authors: The Institute for Liver and Digestive Health, University College London, London, United Kingdom.
authors: Shahriar
authors: S
authors: Behboudi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003710:Demography; D058851:GPI-Linked Proteins / Q000097:blood / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000097:blood; D000090204:Mesothelin; D008875:Middle Aged; D008969:Molecular Sequence Data; D010190:Pancreatic Neoplasms / Q000097:blood / Q000276:immunology*; D010455:Peptides / Q000737:chemistry / Q000276:immunology
chemical_list: D058851:GPI-Linked Proteins; D010455:Peptides; D016753:Interleukin-10; D007371:Interferon-gamma; D000090204:Mesothelin