Journal Article

DKFZ-2017-03389

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Tumor-specific cytotoxic T lymphocyte activity determines colorectal cancer patient prognosis.

Reissfelder, C. ; Stamova, S. ; Gossmann, C. ; Braun, M. ; Bonertz, A. ; Walliczek, U. ; Grimm, M. ; Rahbari, N. N. ; Koch, M. ; Saadati, M.DKFZ* ; Benner, A.DKFZ* ; Büchler, M. W. ; Jäger, D. ; Halama, N. ; Khazaie, K. ; Weitz, J. ; Beckhove, P. (Last author)DKFZ*

2015
ASCJ Ann Arbor, Mich.

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Please use a persistent id in citations: doi:10.1172/JCI74894

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.

Keyword(s): Neoplasm Proteins ; TNF protein, human ; Tumor Necrosis Factor-alpha

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Contributing Institute(s):

1. Translationale Immunologie (D015)
2. Biostatistik (C060)

Research Program(s):

1. 314 - Tumor immunology (POF3-314) (POF3-314)

Appears in the scientific report 2015

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Database coverage:
; BIOSIS Previews ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 10 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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