In conclusion, our study showed that GGCT contributed to malignant progression and upregulation of PD-L1 expression of endometrial carcinoma, and may be a potential target for treatment of endometrial carcinoma.
Immune check-point inhibitors such as anti-PD-1/PD-L1 antibodies have proved successful for mismatch repair-deficient endometrial cancers and HPV-targeted therapies are under development for HPV-related malignancies.
This case indicates the potential existence of an endometrial cancer subtype that is sensitive to immune checkpoint blockade based on mechanisms other than those driven by MMR deficiency or PD-L1 positivity.
The exception has been the PD-1 inhibitor pembrolizumab in microsatellite instability high (MSI-H) or mismatch repair-deficient (dMMR) advanced endometrial cancers, highlighted by the recent conditional approval of pembrolizumab in recurrent/metastatic PD-L1-positive cervical cancers and the accelerated approval of pembrolizumab and lenvatinib in microsatellite stable (MSS) or mismatch repair-proficient (pMMR) advanced endometrial cancer.
We evaluated the expression of PD-L1 in carcinoma cells (Ca) and immune cells (ICs) across histopathologic and The Cancer Genome Atlas (TCGA) molecular subgroups of endometrial carcinoma (EC).
The purpose of this study was to determine if a subset of microsatellite-stable endometrioid endometrial carcinomas have higher immune cell infiltrates and/or expression of PD-L1.
Pembrolizumab has been approved for relapsed cervical cancer with programmed death ligand 1 positivity and relapsed solid tumors with mismatch repair deficiency, which applies to 30% of endometrial cancers.
The high PD-L1/CD8 ratio and the high expression of PD-L1 on immune cells were independent poor prognostic factors for PFS in endometrial cancer, providing insights into the tumor microenvironment.
Mutations in polymerase ε (POLE), a DNA polymerase involved in DNA replication and repair, have been investigated in endometrial cancers and response to programmed cell death protein 1 (PD-1)/PD-1 ligand (PD-L1) immunotherapy.
Activity of PD-1 and PD-L1 inhibitors has been demonstrated in ovarian, endometrial, and cervical cancer, with a tolerable side effect profile and the highest response rate seen in mismatch repair-deficient endometrial cancers.
Immune checkpoint inhibitors have demonstrated a very impressive safety profile and anti-tumor activity in patients with programmed death-ligand 1 (PD-L1) positive endometrial cancer who were pre-treated with chemotherapy.
Loss of MMR proteins has been shown to correlate with tumoral PD-L1 expression in colorectal and endometrial carcinomas, but the association between expression of MMR proteins and PD-L1 has not previously been studied in breast carcinoma, where MMR deficiency is less common.
Breast cancer (BRCA)-mutated high-grade serous ovarian cancers, clear cell ovarian cancers with microsatellite instability (MSI), POLE ultramutated and MSI hypermutated endometrial cancers are likely to be sensitive to programmed cell death (PD-1)/PD-ligand 1 (PD-L1) pathway blockade, since these tumors show increased neoantigen load, increased CD8<sup>+</sup> TIL number and PD-1 and PD-L1 overexpression.