Tumor-specific cytotoxic T lymphocyte activity determines colorectal cancer patient prognosis

作者：Reissfelder Christoph; Stamova Slava; Gossmann Christina; Braun Marion; Bonertz Andreas; Walliczek Ute; Grimm Mario; Rahbari Nuh N; Koch Moritz; Saadati Mara; Benner Axel; Buechler Markus W; Jaeger Dirk; Halama Niels; Khazaie Khashayarsha; Weitz Juergen; Beckhove Philipp^*

来源：Journal of Clinical Investigation, 2015, 125(2): 739-751.

DOI：10.1172/JCI74894

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-alpha expression delineates a population of tumor antigen-specific (TA-specific) cytotoxic T lymphocytes (CTLs) present within tumors from patients with CRC. Upregulation of TNF-alpha expression in TILs strongly correlated with an increase in the total amount of intratumoral TNF-alpha, 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-alpha 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-alpha, which is indicative of T cell function, as a prognostic parameter for CRC.

• 出版日期2015-2
• 单位西北大学