Does immunotherapy hold great promise in endometrial cancer care?

Abstract

Endometrial cancer (EC) is a hormonally driven malignancy with a strikingly uneven global distribution, interestingly occurring far more frequently in developed countries. Central to its pathogenesis is endocrine imbalance, which is most notably due to prolonged exposure to unopposed oestrogen, which fuels tumour initiation and progression. The dynamic interplay between oestrogen and progesterone signalling shapes disease biology and underpins the widespread use of hormonal therapies, particularly in early-stage disease and in patients who are not surgical candidates. Current EC management relies on a multimodal approach, integrating surgery, radiotherapy, hormonal therapy, and chemotherapy. However, the therapeutic landscape is rapidly evolving. Ongoing clinical trials are investigating innovative immunotherapeutic strategies, including biomarker-driven treatments, rational combination regimens, and adoptive cellular therapies. Immune checkpoint inhibitors have already demonstrated clinical benefit in mismatch repair-deficient EC. In parallel, cancer vaccines targeting tumour-associated antigens such as folate-binding protein (FBP), along with emerging modalities like CAR T-cell therapy, are being explored for their potential to reduce recurrence and improve long-term outcomes. Recent advances have highlighted the PI3K/AKT/mTOR signalling cascade as a key therapeutic target, offering opportunities to enhance the effectiveness of endocrine treatments. At the same time, growing evidence underscores the importance of crosstalk between hormonal dysregulation and immune mechanisms within the tumour microenvironment, a relationship that profoundly influences tumour behaviour and therapeutic response. In this review, we present a comprehensive overview of the current state of EC management and emerging therapeutic directions, with particular emphasis on treatment options available in Poland, the authors' country of origin.