Immunity
Volume 44, Issue 3, 15 March 2016, Pages 698-711
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Article
Integrative Analyses of Colorectal Cancer Show Immunoscore Is a Stronger Predictor of Patient Survival Than Microsatellite Instability

https://doi.org/10.1016/j.immuni.2016.02.025Get rights and content
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Highlights

  • MSI and a subgroup of MSS patients have high intratumoral adaptive immune gene expression

  • Functional effector anti-frameshift mutation CTLs kill tumor cells in MSI patients

  • Genetic evidence of immunoediting in human CRC, in particular for MSI patients

  • Immunoscore gives an indicator of tumor recurrence and survival beyond MSI staging

Summary

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.

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