Tumor immunology and immunotherapy for endometrial cancer

Recent clinical trials show the efficacy of immune checkpoint inhibitors (ICIs) or a combination of ICI and poly (ADP-ribose) polymerase (PARP) inhibitors for advanced or recurrent endometrial cancer. However, the basis for such treatment effects remains unclear, hindering the advancement of personalized therapy.

This review includes a detailed interpretation of subgroup analysis data from phase III clinical trials for endometrial cancer evaluating the efficacy of chemotherapy plus ICIs (NRG-GY018, RUBY, AtTEnd, KEYNOTE-B21) or chemotherapy plus ICI with/without olaparib (DUO-E). We focused on the relationship between obesity, the effect of PARP inhibitors, and tumor immunity in endometrial cancer, searched for relevant literature published from 2000 to 2024 in PubMed, and conducted a narrative review.

Chemotherapy plus ICI is appropriate for dMMR. Chemotherapy plus ICI and PARP inhibitor may be appropriate for TP53abn type or serous carcinoma because PARP inhibitor enhances the efficacy of ICI by activating the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway. Obese patients may benefit more from ICIs, and this appears to cause the variation in efficacy between regions/countries. Administration for measurable disease appears important to increase the effect of ICIs. Diet and exercise may also be important factors.