Reduced PD1/PDL1 expression in KRAS-mutant versus wildtype (MSI-H) CRC and association of Wnt pathway corepressor TLE-3

Authors:

Namrata Vijayvergia, Julie Innocent, Aarti Khushal Bhatia, Raji Shameem, Joanne Xiu, Zoran Gatalica, Sergei Grivennikov, Wafik S. El-Deiry

Background

MSI-H CRC comprises ~15% of CRC & has higher PD-1 & PD-L1 (P(+)) expression in CD4+ lymphocytes & tumor cells, respectively, compared to non-MSI-H CRC. Immune-checkpoint inhibitor therapy is being tested in clinical trials for MSI-H CRC (NCT02060188, NCT01876511). Human homologue of Groucho, Transducin-like-Enhancer of Split orthologue (TLE-3), inhibits Wnt signaling by competition with b-catenin for LEF/TCF binding. We investigated different biomarkers that may characterize P(+) MSI-H CRC.

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