Mismatch repair deficient bowel cancers do better partly because they are full of immune cells. When the immune cells are counted directly, the count predicts outcome better than the repair status does.
Significant differences in mutational patterns, chromosomal instability and gene expression were found that correlated with microsatellite instability status. A prominent immune gene expression programme was observed in microsatellite-unstable tumours and in a subgroup of microsatellite-stable tumours. Unstable tumours had increased frameshift mutations, genetic evidence of immunoediting, higher densities of T-helper-1, effector-memory and in situ proliferating T cells and of inhibitory PD-1 and PD-L1 cells, high Immunoscores, and infiltration with mutation-specific cytotoxic T cells. In multivariate analysis, Immunoscore was superior to microsatellite instability in predicting disease-specific recurrence and survival.
It explains the good prognosis of mismatch repair deficient disease as an immune effect rather than a repair effect, and identifies the microsatellite-stable tumours with an immune programme as the group worth trying immunotherapy in.
Shares Institut Curie, Tumour microenvironment (TME), The cancer-immunity cycle, Immunohistochemistry (IHC).
Shares Cell, Antigen presentation & immune editing, Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Neoantigen.
Shares Tumour microenvironment (TME), The cancer-immunity cycle, Immunohistochemistry (IHC), Histopathology & immunohistochemistry.
Shares Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Immunohistochemistry (IHC), Histopathology & immunohistochemistry, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR).
Shares Antigen presentation & immune editing, Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Neoantigen, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR).
Shares Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Neoantigen, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), PD-1.
Shares Antigen presentation & immune editing, Neoantigen, The cancer-immunity cycle.
Shares Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Neoantigen, The cancer-immunity cycle, Colorectal cancer.