TY  - JOUR
AU  - Reissfelder, Christoph
AU  - Stamova, Slava
AU  - Gossmann, Christina
AU  - Braun, Marion
AU  - Bonertz, Andreas
AU  - Walliczek, Ute
AU  - Grimm, Mario
AU  - Rahbari, Nuh N
AU  - Koch, Moritz
AU  - Saadati, Maral
AU  - Benner, Axel
AU  - Büchler, Markus W
AU  - Jäger, Dirk
AU  - Halama, Niels
AU  - Khazaie, Khashayarsha
AU  - Weitz, Jürgen
AU  - Beckhove, Philipp
TI  - Tumor-specific cytotoxic T lymphocyte activity determines colorectal cancer patient prognosis.
JO  - The journal of clinical investigation
VL  - 125
IS  - 2
SN  - 0021-9738
CY  - Ann Arbor, Mich.
PB  - ASCJ
M1  - DKFZ-2017-03389
SP  - 739 - 751
PY  - 2015
AB  - 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.
KW  - Neoplasm Proteins (NLM Chemicals)
KW  - TNF protein, human (NLM Chemicals)
KW  - Tumor Necrosis Factor-alpha (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:25562322
C2  - pmc:PMC4319435
DO  - DOI:10.1172/JCI74894
UR  - https://inrepo02.dkfz.de/record/127364
ER  -