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T cell-inflamed phenotype and increased Foxp3 expression in infiltrating T-cells of mismatch-repair deficient endometrial cancers
- Source :
- Mod Pathol
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
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.
- Subjects :
- Adult
0301 basic medicine
Pathology
medicine.medical_specialty
medicine.medical_treatment
T cell
Cell
chemical and pharmacologic phenomena
Article
Pathology and Forensic Medicine
03 medical and health sciences
Lymphocytes, Tumor-Infiltrating
0302 clinical medicine
Immune system
Germline mutation
Neoplastic Syndromes, Hereditary
T-Lymphocyte Subsets
Humans
Medicine
Aged
Aged, 80 and over
Inflammation
Brain Neoplasms
business.industry
Endometrial cancer
FOXP3
Forkhead Transcription Factors
Immunotherapy
Middle Aged
medicine.disease
Endometrial Neoplasms
Phenotype
030104 developmental biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
Cancer research
Female
DNA mismatch repair
Colorectal Neoplasms
business
Subjects
Details
- ISSN :
- 08933952
- Volume :
- 32
- Database :
- OpenAIRE
- Journal :
- Modern Pathology
- Accession number :
- edsair.doi.dedup.....f5be5a56467cae8bd1897bb7527a3fff