Janneke S Hoogstad-van Evert

TIGIT blockade enhances functionality of peritoneal NK cells with altered expression of DNAM-1/TIGIT/CD96 checkpoint molecules in ovarian cancer

Advanced ovarian cancer (OC) patients have a poor 5-year survival of only 28%, emphasizing the medical need for improved therapies. Adjuvant immunotherapy could be an attractive approach since OC is an immunogenic disease and the presence of tumor-infiltrating lymphocytes has shown to positively correlate with patient survival. Among these infiltrating lymphocytes are natural killer (NK) cells, key players involved in tumor targeting, initiated by signaling via activating and inhibitory receptors. Here, we investigated the role of the DNAM-1/TIGIT/CD96 axis in the anti-tumor response of NK cells toward OC. Ascites-derived NK cells from advanced OC patients showed lower expression of activating receptor DNAM-1 compared to healthy donor peripheral blood NK cells, while inhibitory receptor TIGIT and CD96 expression was equal or higher, respectively. This shift to a more inhibitory phenotype could also be induced

CD34 + progenitor-derived NK cell and gemcitabine combination therapy increases killing of ovarian cancer cells in NOD/SCID/IL2Rg null mice

Combining natural killer (NK) cell adoptive transfer with tumor-sensitizing chemotherapy is an attractive approach against recurrent ovarian cancer (OC), as OC is sensitive to NK cell-mediated immunity. Previously, we showed that CD34

Real-world performance of the Assessment of Different NEoplasias in the adneXa (ADNEX) model for the pre-operative classification of ovarian tumors.

To predict the risk of malignancy in ovarian tumors, the multi-class risk prediction Assessment of Different NEoplasias in the adneXa (ADNEX) model of the International Ovarian Tumor Analysis group is used internationally. This study aimed to perform an external validation of this model in a real-world clinical setting in the Netherlands. A multi-center, retrospective diagnostic accuracy study was performed. Women aged ≥18 years who attended the outpatient clinic between May 2020 and December 2021 and had a first ultrasound assessment for an ovarian tumor with application of the International Ovarian Tumor Analysis ADNEX model were included. The reference standard was the pathology result in case of surgery or follow-up with ultrasound according to the current Dutch guideline in case of conservative management. Of the 363 women included, 286 (78.8%) had benign, 24 (6.6%) had borderline, and 53 (14.6%) had malignant pathology. Most (62.5%) of the included patients underwent surgery. The area under the receiver operating characteristic (ROC) curve was 0.92 (95% CI 0.89 to 0.96) if borderline tumors were considered malignant and 0.93 (95% CI 0.89 to 0.96) if borderline tumors were considered benign. Cutoff values between 7% and 14% yielded the highest Youden index. The model was moderately able to differentiate between malignant histologic sub-types. The ADNEX model showed excellent diagnostic performance in daily clinical practice and retained its value in a population in which a proportion of patients were treated with conservative management.