%0 Journal Article
%A Reissfelder, Christoph
%A Stamova, Slava
%A Gossmann, Christina
%A Braun, Marion
%A Bonertz, Andreas
%A Walliczek, Ute
%A Grimm, Mario
%A Rahbari, Nuh N
%A Koch, Moritz
%A Saadati, Maral
%A Benner, Axel
%A Büchler, Markus W
%A Jäger, Dirk
%A Halama, Niels
%A Khazaie, Khashayarsha
%A Weitz, Jürgen
%A Beckhove, Philipp
%T Tumor-specific cytotoxic T lymphocyte activity determines colorectal cancer patient prognosis.
%J The journal of clinical investigation
%V 125
%N 2
%@ 0021-9738
%C Ann Arbor, Mich.
%I ASCJ
%M DKFZ-2017-03389
%P 739 - 751
%D 2015
%X 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.
%K Neoplasm Proteins (NLM Chemicals)
%K TNF protein, human (NLM Chemicals)
%K Tumor Necrosis Factor-alpha (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:25562322
%2 pmc:PMC4319435
%R 10.1172/JCI74894
%U https://inrepo02.dkfz.de/record/127364