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000127364 0247_ $$2doi$$a10.1172/JCI74894
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000127364 0247_ $$2pmc$$apmc:PMC4319435
000127364 0247_ $$2ISSN$$a0021-9738
000127364 0247_ $$2ISSN$$a1558-8238
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000127364 037__ $$aDKFZ-2017-03389
000127364 041__ $$aeng
000127364 082__ $$a610
000127364 1001_ $$aReissfelder, Christoph$$b0
000127364 245__ $$aTumor-specific cytotoxic T lymphocyte activity determines colorectal cancer patient prognosis.
000127364 260__ $$aAnn Arbor, Mich.$$bASCJ$$c2015
000127364 3367_ $$2DRIVER$$aarticle
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000127364 520__ $$aThe 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.
000127364 536__ $$0G:(DE-HGF)POF3-314$$a314 - Tumor immunology (POF3-314)$$cPOF3-314$$fPOF III$$x0
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000127364 650_7 $$2NLM Chemicals$$aNeoplasm Proteins
000127364 650_7 $$2NLM Chemicals$$aTNF protein, human
000127364 650_7 $$2NLM Chemicals$$aTumor Necrosis Factor-alpha
000127364 7001_ $$aStamova, Slava$$b1
000127364 7001_ $$aGossmann, Christina$$b2
000127364 7001_ $$aBraun, Marion$$b3
000127364 7001_ $$aBonertz, Andreas$$b4
000127364 7001_ $$aWalliczek, Ute$$b5
000127364 7001_ $$aGrimm, Mario$$b6
000127364 7001_ $$aRahbari, Nuh N$$b7
000127364 7001_ $$aKoch, Moritz$$b8
000127364 7001_ $$0P:(DE-He78)609d3f1c1420bf59b2332eeab889cb74$$aSaadati, Maral$$b9$$udkfz
000127364 7001_ $$0P:(DE-He78)e15dfa1260625c69d6690a197392a994$$aBenner, Axel$$b10$$udkfz
000127364 7001_ $$aBüchler, Markus W$$b11
000127364 7001_ $$aJäger, Dirk$$b12
000127364 7001_ $$aHalama, Niels$$b13
000127364 7001_ $$aKhazaie, Khashayarsha$$b14
000127364 7001_ $$aWeitz, Jürgen$$b15
000127364 7001_ $$0P:(DE-He78)1732377f6242a18280bc6aaa196988d1$$aBeckhove, Philipp$$b16$$eLast author$$udkfz
000127364 773__ $$0PERI:(DE-600)2018375-6$$a10.1172/JCI74894$$gVol. 125, no. 2, p. 739 - 751$$n2$$p739 - 751$$tThe @journal of clinical investigation$$v125$$x0021-9738$$y2015
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000127364 9141_ $$y2015
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