ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2019
T cell-inflamed phenotype and increased Foxp3 expression in infiltrating T-cells of mismatch-repair deficient endometrial cancers.
Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- Durvalumab plus carboplatin/paclitaxel followed by durvalumab with or without olaparib as first-line treatment for newly diagnosed advanced or recurrent endometrial cancer: Japan subset from the phase III DUO-E trial.Journal of gynecologic oncology · 2025Trial
- Foxp3Current gene therapy · 2026Article
- Mismatch Repair as a Dynamic and Clinically Actionable Vulnerability in Cancer.Cancer research · 2025Review
- Germline whole-exome sequencing revealsJournal for immunotherapy of cancer · 2025Article
- Activated immune infiltrates expand opportunities for targeted therapy in p53-abnormal endometrial carcinoma.The Journal of pathology · 2025Article
- A pilot study investigating the effect of pembrolizumab on the tumoral immunoprofile of newly diagnosed mullerian cancers.Gynecologic oncology reports · 2025Article
- Association of peripheral monocytic myeloid-derived suppressor cells with molecular subtypes in single-center endometrial cancer patients receiving carboplatin + paclitaxel/avelumab (MITO-END3 trial).Cancer immunology, immunotherapy : CII · 2025Article
- Association of glutaminase expression with immune-suppressive tumor microenvironment, clinicopathologic features, and clinical outcomes in endometrial cancer.International journal of gynecological cancer : official journal of the International Gynecological Cancer Society · 2024Article
- Molecular Classification of Endometrial Cancer and Its Impact on Therapy Selection.International journal of molecular sciences · 2024Review
- Mismatch repair geneFrontiers in immunology · 2024Article
- Expression of PD-1 and PD-L1 in Endometrial Cancer: Molecular and Clinical Significance.International journal of molecular sciences · 2023Review
- New insights for gynecological cancer therapies: from molecular mechanisms and clinical evidence to future directions.Cancer metastasis reviews · 2023Review
- Construction of the novel immune risk scoring system related to CD8Cancer cell international · 2023Article
- Presence of regulatory T-cells in endometrial cancer predicts poorer overall survival and promotes progression of tumor cells.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- T-Cell Density at the Invasive Margin and Immune Phenotypes Predict Outcome in Vulvar Squamous Cell Cancer.Cancers · 2022Article
- Overcoming resistance to αPD-1 of MMR-deficient tumors with high tumor-induced neutrophils levels by combination of αCTLA-4 and αPD-1 blockers.Journal for immunotherapy of cancer · 2022Article
- Current Prognostic and Predictive Biomarkers for Endometrial Cancer in Clinical Practice: Recommendations/Proposal from the Italian Study Group.Frontiers in oncology · 2022Review
- The immunologic tumor microenvironment in endometrioid endometrial cancer in the morphomolecular context: mutual correlations and prognostic impact depending on molecular alterations.Cancer immunology, immunotherapy : CII · 2021Article
- Analysis of tumor mutation burden combined with immune infiltrates in endometrial cancer.Annals of translational medicine · 2021Article
- PD-L1 Expression Is an Independent Marker for Lymph Node Metastasis in Middle Eastern Endometrial Cancer.Diagnostics (Basel, Switzerland) · 2021Article
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Funding
Abstract
Mismatch repair-deficient endometrial cancers have a high somatic mutation burden, suggesting that patients with these tumors may benefit from immunotherapy. Elucidating the immune suppressive mechanisms of mismatch repair-deficient endometrial cancers is fundamental to developing future immune-based interventions. This study aimed to determine the immune cell populations associated with mismatch repair-deficient endometrial cancers, especially focusing on targetable regulatory pathways of the immune response. A total of 76 endometrial cancer hysterectomy specimens were evaluated for tumor-infiltrating immune cells by immunohistochemistry. Immune specific markers were used to evaluate each specimen for the number of CD8 + cytotoxic T lymphocytes, forkhead-box P3 (FoxP3) + regulatory T cells, CD68 + tumor-associated macrophages, as well as programmed death-1 (PD-1) + immune cells, and the percentage of programmed death ligand-1 (PD-L1) + immune cells. Mismatch repair-deficient tumors exhibited a significantly higher number of CD8 + cytotoxic T lymphocytes (p = 0.0006), FoxP3 + regulatory T cells (p = 0.0003), PD-1 + immune cells (p = 0.0069), and a higher percentage of PD-L1 + immune cells (p = 0.0007) occupying the tumor compared to mismatch repair-proficient endometrial cancers. There was no significant difference in CD68 + tumor-associated macrophages infiltration between the two groups. Endometrial cancers with tumor PD-L1 expression also showed significantly increased infiltration of CD8 + cytotoxic T lymphocytes (p = 0.0002), FoxP3 + regulatory T cells (p = 0.0003), PD-1 + immune cells (p < 0.0001), and PD-L1 + immune cells (p < 0.0001). Endometrial cancers showing mismatch repair-deficiency and PD-L1 expression in tumor cells exhibit a prominent T cell-inflamed phenotype. More importantly, the increased number of FoxP3 + regulatory T cells in mismatch repair-deficient endometrial cancers suggests that combination therapy by targeting both regulatory T cells and immune checkpoints may be warranted to improve clinical efficacy.
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