Study finds a possible explanation for why immunotherapy works well for some cancer patients, but not others yale
Mismatch repair-deficient cancers have varied responses to immune checkpoint blockade . We conducted a phase 2 clinical trial of the PD-1 inhibitor pembrolizumab in 24 patients with MMRd endometrial cancer . Patients with mutational MMRd tumors had higher response rates and longer survival than those with epigenetic MMRd tumors .
Pre-treatment JAK1 mutations were not associated with primary resistance to pembrolizumab. Longitudinal single-cell RNA-seq of circulating immune cells revealed contrasting modes of anti-tumor immunity for mutational vs. epigenetic MMRd cancers. Whereas effector CD8+ T cells correlated with regression of mutational MMRd tumors, activated CD16+ NK cells were associated with ICB-responsive epigenetic MMRd tumors.