title: Proximal signaling responses in peripheral T cells from colorectal cancer patients are affected by high concentrations of circulating prostaglandin E2.
abstract: Patients with colorectal cancer (CRC) have been shown to have elevated levels of circulating prostaglandin E2(PGE2) which promotes cancer progression and suppresses T cell immune responses. In this study we evaluated whether signaling responses in T lymphocytes obtained from peripheral blood of CRC patients were affected by the sustained exposure to increased levels of PGE2. The phosphorylation status of an extended panel of proteins involved in downstream signaling cascades in T cells was profiled at a single cell level both in naïve and antigen-experienced cells after triggering T cell-, prostaglandin- and interleukin-2 receptors. Peripheral T cells from patients with elevated PGE2levels displayed aberrant T cell signaling responses downstream of the T cell receptor (assessed by reduced phosphorylation of CD3ζ and SLP76), and after triggering the IL-2 receptor (assessed by reduced phosphorylation of STAT5) when compared to T cells from CRC patients with lower levels of PGE2and T cells from healthy blood donors. This signaling study of circulating T cells from CRC patients indicates that increased systemic PGE2levels affect proximal T cell responses and confirms phospho-specific flow cytometry to be a valuable tool for revealing signaling signatures in immunological disorders.
authors: Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, P.O. Box 1137 Blindern, 0318 Oslo, Norway; Biotechnology Centre, University of Oslo, P.O. Box 1125 Blindern, 0317 Oslo, Norway.
authors: Kristine
authors: K
authors: Moltu
authors: Biotechnology Centre, University of Oslo, P.O. Box 1125 Blindern, 0317 Oslo, Norway; Department of Gastrointestinal Surgery, Oslo University Hospital, P.O. Box 4956 Nydalen, 0424 Oslo, Norway.
authors: Karen
authors: K
authors: Henjum
authors: Biotechnology Centre, University of Oslo, P.O. Box 1125 Blindern, 0317 Oslo, Norway.
authors: Nikolaus G
authors: NG
authors: Oberprieler
authors: Department of Gastrointestinal Surgery, Oslo University Hospital, P.O. Box 4956 Nydalen, 0424 Oslo, Norway.
authors: Bjørn A
authors: BA
authors: Bjørnbeth
authors: Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, P.O. Box 1137 Blindern, 0318 Oslo, Norway; Biotechnology Centre, University of Oslo, P.O. Box 1125 Blindern, 0317 Oslo, Norway; Department of Infectious Diseases, Oslo University Hospital, P.O. Box 4956 Nydalen, 0424 Oslo, Norway; K.G. Jebsen Centre for Cancer Immunotherapy, Biotechnology Centre, University of Oslo, P.O. Box 1125 Blindern, 0317 Oslo, Norway; K.G. Jebsen Inflammation Research Centre, Centre for Molecular Medicine Norway, University of Oslo, P.O. Box 1137 Blindern, 0318 Oslo, Norway. Electronic address: kjetil.tasken@ncmm.uio.no.
authors: Kjetil
authors: K
authors: Taskén
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D049109:Cell Proliferation; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000276:immunology*; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D015232:Dinoprostone
keywords: Colorectal cancer; PGE(2); Phospho-specific flow cytometry; T cell signaling