apyrase and Carcinoma--Ovarian-Epithelial

Phenotypic characterization of γδ T cells in the MALs (malignant ascites lymphocytes), TILs (tumor infiltrating lymphocytes), and PBLs (peripheral blood lymphocytes) of ovarian cancer (OvCA) patients is lacking. Therefore, we quantified γδ T cell prevalence in MAL, TIL, and PBL specimens from

Topics: Apyrase; Carcinoma, Ovarian Epithelial; Female; Hepatitis A Virus Cellular Receptor 2; Humans; Ovarian Neoplasms; Programmed Cell Death 1 Receptor; Receptors, Immunologic

Responses to immunotherapy vary between different cancer types and sites. Here, we aimed to investigate features of exhaustion and activation in tumor-infiltrating CD8 T cells at both the primary and metastatic sites in epithelial ovarian cancer.. Tumor tissues and peripheral blood were obtained from 65 patients with ovarian cancer. From these samples, we isolated tumor-infiltrating lymphocytes (TILs) and peripheral blood mononuclear cells. These cells were used for immunophenotype using multicolor flow cytometry, gene expression profile using RNA sequencing and ex vivo functional restoration assays.. We found that CD39. Severely exhausted PD-1

Topics: Apyrase; Carcinoma, Ovarian Epithelial; CD8-Positive T-Lymphocytes; Female; Humans; Immune Checkpoint Inhibitors; Middle Aged; Neoplasm Metastasis; Prospective Studies; Tumor Necrosis Factor Receptor Superfamily, Member 9

The cell surface nucleotidase CD73 is an immunosuppressive enzyme involved in tumor progression and metastasis. Although preclinical studies suggest that CD73 can be targeted for cancer treatment, the clinical impact of CD73 in ovarian cancer remains unclear. In this study, we investigated the prognostic value of CD73 in high-grade serous (HGS) ovarian cancer using gene and protein expression analyses. Our results demonstrate that high levels of CD73 are significantly associated with shorter disease-free survival and overall survival in patients with HGS ovarian cancer. Furthermore, high levels of CD73 expression in ovarian tumor cells abolished the good prognosis associated with intraepithelial CD8(+) cells. Notably, CD73 gene expression was highest in the C1/stromal molecular subtype of HGS ovarian cancer and positively correlated with an epithelial-to-mesenchymal transition gene signature. Moreover, in vitro studies revealed that CD73 and extracellular adenosine enhance ovarian tumor cell growth as well as expression of antiapoptotic BCL-2 family members. Finally, in vivo coinjection of ID8 mouse ovarian tumor cells with mouse embryonic fibroblasts showed that CD73 expression in fibroblasts promotes tumor immune escape and thereby tumor growth. In conclusion, our study highlights a role for CD73 as a prognostic marker of patient survival and also as a candidate therapeutic target in HGS ovarian cancers.

Topics: 5'-Nucleotidase; Adult; Aged; Aged, 80 and over; Animals; Antigens, CD; Apyrase; Biomarkers, Tumor; Carcinoma, Ovarian Epithelial; Cell Line, Tumor; Cell Proliferation; Disease-Free Survival; Epithelial-Mesenchymal Transition; Female; Fibroblasts; Gene Expression Regulation, Neoplastic; GPI-Linked Proteins; Humans; Mice; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Proto-Oncogene Proteins c-bcl-2; RNA Interference; RNA, Small Interfering; Tumor Escape