Dual mechanism of immune escape shapes the genetic and immunogenic landscape of mismatch repair-deficient colorectal tumours - PubMed
5 hours ago
- #Immune Escape
- #MMRd Colorectal Cancer
- #Immunoediting
- Immune pressure in immunocompetent hosts reduces tumor incidence by selectively eliminating early neoplastic clones with immunogenic mutations, a process consistent with antigen-specific immunoediting.
- Tumors in immunocompetent hosts develop a suppressive microenvironment, characterized by reduced cytotoxic lymphocytes and elevated immune checkpoint proteins, promoting local immunosuppression.
- Tumors from immunodeficient mice show higher mutational burden, greater genetic diversity, and enrichment of mutations that encode neoantigens capable of eliciting CD8+ T cell responses.
- Human MSI-H colorectal cancers retain immunogenic mutations, display elevated mutational burden, reduced effector immune infiltration, and expression of immune checkpoint proteins, validating the mouse model findings.
- A dual mechanism of immune escape involving immunoediting and local immunosuppression allows MMRd colorectal tumors to persist despite immune recognition, explaining their immune-rich yet progressive nature.