Mismatch repair and clinical response to immune checkpoint inhibitors in endometrial cancer

Lay Summary Endometrial cancer is common, and a subset recurs and requires additional treatment. Some of these are recognized as being susceptible to immune therapies and are said to have mismatch repair deficiency (dMMR). However, this clinical trial highlights which cases are more likely to respond well: those containing mutations in genes known as Lynch genes and also some with mutations in POLE/POLD1 (ultra-hypermutation genes). In contrast, the majority of dMMR endometrial cancers have silencing or DNA methylation of one of these genes, MLH1, and do not seem to be as responsive to single-agent immune therapy. The availability of combination therapies may be important to consider for these women.

Automated summary

Endometrial cancer patients with Lynch gene or POLE/POLD1 gene mutations are more likely to respond well to immune therapy, while those with silencing of the MLH1 gene may not be as responsive. Combination therapies may be important to consider for these patients.