Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Mlecnik, B; Bindea, G; Angell, HK; Maby, P; Angelova, M; Tougeron, D; Church, SE; Lafontaine, L; Fischer, M; Fredriksen, T; Sasso, M; Bilocq, AM; Kirilovsky, A; Obenauf, AC; Hamieh, M; Berger, A; Bruneval, P; Tuech, JJ; Sabourin, JC; Le Pessot, F; Mauillon, J; Rafii, A; Laurent-Puig, P; Speicher, MR; Trajanoski, Z; Michel, P; Sesboüe, R; Frebourg, T; Pagès, F; Valge-Archer, V; Latouche, JB; Galon, J.
Integrative Analyses of Colorectal Cancer Show Immunoscore Is a Stronger Predictor of Patient Survival Than Microsatellite Instability.
Immunity. 2016; 44(3):698-711
Doi: 10.1016/j.immuni.2016.02.025
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- Co-Autor*innen der Med Uni Graz
- Obenauf Anna Christina
- Speicher Michael
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- Abstract:
- Microsatellite instability in colorectal cancer predicts favorable outcomes. However, the mechanistic relationship between microsatellite instability, tumor-infiltrating immune cells, Immunoscore, and their impact on patient survival remains to be elucidated. We found significant differences in mutational patterns, chromosomal instability, and gene expression that correlated with patient microsatellite instability status. A prominent immune gene expression was observed in microsatellite-instable (MSI) tumors, as well as in a subgroup of microsatellite-stable (MSS) tumors. MSI tumors had increased frameshift mutations, showed genetic evidence of immunoediting, had higher densities of Th1, effector-memory T cells, in situ proliferating T cells, and inhibitory PD1-PDL1 cells, had high Immunoscores, and were infiltrated with mutation-specific cytotoxic T cells. Multivariate analysis revealed that Immunoscore was superior to microsatellite instability in predicting patients' disease-specific recurrence and survival. These findings indicate that assessment of the immune status via Immunoscore provides a potent indicator of tumor recurrence beyond microsatellite-instability staging that could be an important guide for immunotherapy strategies. Copyright © 2016 Elsevier Inc. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Aged -
- Aged, 80 and over -
- Cells, Cultured -
- Colorectal Neoplasms - diagnosis
- Colorectal Neoplasms - mortality
- Cytotoxicity Tests, Immunologic -
- DNA Mutational Analysis -
- Female -
- Frameshift Mutation - genetics
- Humans -
- Immunoassay - methods
- Immunologic Memory -
- Male -
- Microsatellite Instability -
- Microsatellite Repeats -
- Pathology, Molecular - methods
- Predictive Value of Tests -
- Prognosis -
- Survival Analysis -
- T-Lymphocyte Subsets - immunology
- Th1 Cells - immunology
- Transcriptome -