% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Reissfelder:127364,
      author       = {C. Reissfelder and S. Stamova and C. Gossmann and M. Braun
                      and A. Bonertz and U. Walliczek and M. Grimm and N. N.
                      Rahbari and M. Koch and M. Saadati$^*$ and A. Benner$^*$ and
                      M. W. Büchler and D. Jäger and N. Halama and K. Khazaie
                      and J. Weitz and P. Beckhove$^*$},
      title        = {{T}umor-specific cytotoxic {T} lymphocyte activity
                      determines colorectal cancer patient prognosis.},
      journal      = {The journal of clinical investigation},
      volume       = {125},
      number       = {2},
      issn         = {0021-9738},
      address      = {Ann Arbor, Mich.},
      publisher    = {ASCJ},
      reportid     = {DKFZ-2017-03389},
      pages        = {739 - 751},
      year         = {2015},
      abstract     = {The composition of tumor-targeted T cell infiltrates is a
                      major prognostic factor in colorectal cancer (CRC) outcome;
                      however, the functional role of these populations in
                      prolonging patient survival remains unclear. Here, we
                      evaluated 190 patients with CRC for the presence of
                      functionally active tumor-infiltrating lymphocytes (TILs),
                      the tumor specificity of these TILs, and the correlation
                      between patient TILs and long-term survival. Using
                      intracytoplasmic cytokine staining in conjunction with HLA
                      multimers loaded with tumor peptide and antigen-specific
                      cytokine secretion assays, we determined that TNF-α
                      expression delineates a population of tumor antigen-specific
                      (TA-specific) cytotoxic T lymphocytes (CTLs) present within
                      tumors from patients with CRC. Upregulation of TNF-α
                      expression in TILs strongly correlated with an increase in
                      the total amount of intratumoral TNF-α, which is indicative
                      of tumor-specific CTL activity. Moreover, a retrospective
                      multivariate analysis of 102 patients with CRC, which had
                      multiple immune parameters evaluated, revealed that
                      increased TNF-α concentration was an independent prognostic
                      factor. Together, these results indicate that the prognostic
                      impact of T cell infiltrates for CRC maybe largely based on
                      subpopulations of active TA-specific T cells within the
                      tumor, suggesting causal implication for these cells in
                      patient survival. Additionally, these results support the
                      use of intratumoral TNF-α, which is indicative of T cell
                      function, as a prognostic parameter for CRC.},
      keywords     = {Neoplasm Proteins (NLM Chemicals) / TNF protein, human (NLM
                      Chemicals) / Tumor Necrosis Factor-alpha (NLM Chemicals)},
      cin          = {D015 / C060},
      ddc          = {610},
      cid          = {I:(DE-He78)D015-20160331 / I:(DE-He78)C060-20160331},
      pnm          = {314 - Tumor immunology (POF3-314)},
      pid          = {G:(DE-HGF)POF3-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:25562322},
      pmc          = {pmc:PMC4319435},
      doi          = {10.1172/JCI74894},
      url          = {https://inrepo02.dkfz.de/record/127364},
}