Dendritic-cells (DCs) have received considerable attention as potential targets for the development of anticancer vaccines. DC-based anticancer vaccination relies on patient-derived DCs pulsed with a source of tumorassociated antigens (TAAs) in the context of standardized maturation-cocktails, followed by their reinfusion. Extensive evidence has confirmed that DC-based vaccines can generate TAA-specific, cytotoxic T cells. Nonetheless, clinical efficacy of DC-based vaccines remains suboptimal, reflecting the widespread immunosuppression within tumors. Thus, clinical interest is being refocused on DC-based vaccines as combinatorial partners for T cell-targeting immunotherapies. Here, we summarize the most recent preclinical/clinical development of anticancer DC vaccination and discuss future perspectives for DC-based vaccines in immunooncology.

ObjectiveTo evaluate the performance of diagnostic prediction models for ovarian malignancy in all patients with an ovarian mass managed surgically or conservatively.DesignMulticentre cohort study.Setting36 oncology referral centres (tertiary centres with a specific gynaecological oncology unit) or other types of centre.ParticipantsConsecutive adult patients presenting with an adnexal mass between January 2012 and March 2015 and managed by surgery or follow-up.Main outcome measuresOverall and centre specific discrimination, calibration, and clinical utility of six prediction models for ovarian malignancy (risk of malignancy index (RMI), logistic regression model 2 (LR2), simple rules, simple rules risk model (SRRisk), assessment of different neoplasias in the adnexa (ADNEX) with or without CA125). ADNEX allows the risk of malignancy to be subdivided into risks of a borderline, stage I primary, stage II-IV primary, or secondary metastatic malignancy. The outcome was based on histology if patients underwent surgery, or on results of clinical and ultrasound follow-up at 12 (±2) months. Multiple imputation was used when outcome based on follow-up was uncertain.ResultsThe primary analysis included 17 centres that met strict quality criteria for surgical and follow-up data (5717 of all 8519 patients). 812 patients (14%) had a mass that was already in follow-up at study recruitment, therefore 4905 patients were included in the statistical analysis. The outcome was benign in 3441 (70%) patients and malignant in 978 (20%). Uncertain outcomes (486, 10%) were most often explained by limited follow-up information. The overall area under the receiver operating characteristic curve was highest for ADNEX with CA125 (0.94, 95% confidence interval 0.92 to 0.96), ADNEX without CA125 (0.94, 0.91 to 0.95) and SRRisk (0.94, 0.91 to 0.95), and lowest for RMI (0.89, 0.85 to 0.92). Calibration varied among centres for all models, however the ADNEX models and SRRisk were the best calibrated. Calibration of the estimated risks for the tumour subtypes was good for ADNEX irrespective of whether or not CA125 was included as a predictor. Overall clinical utility (net benefit) was highest for the ADNEX models and SRRisk, and lowest for RMI. For patients who received at least one follow-up scan (n=1958), overall area under the receiver operating characteristic curve ranged from 0.76 (95% confidence interval 0.66 to 0.84) for RMI to 0.89 (0.81 to 0.94) for ADNEX with CA125.ConclusionsOur study found the ADNEX models and SRRisk are the best models to distinguish between benign and malignant masses in all patients presenting with an adnexal mass, including those managed conservatively.Trial registrationClinicalTrials.gov NCT01698632.

The role of the innate immune system in ovarian cancer is gaining importance. The relevance of tumor-associated macrophages (TAM) is insufficiently understood. In this pilot project, comprising the immunofluorescent staining of 30 biopsies taken from 24 patients with ovarian cancer, we evaluated the presence of total TAM (cluster of differentiation (CD) 68 expression), M1 (major histocompatibility complex (MHC) II expression), and M2 (anti-mannose receptor C type 1 (MRC1) expression), and the blood vessel diameter. We observed a high M1/M2 ratio in low-grade ovarian cancer compared to high-grade tumors, more total TAM and M2 in metastatic biopsies, and a further increase in total TAM and M2 at interval debulking, without beneficial effects of bevacizumab. The blood vessel diameter was indicative for M2 tumor infiltration (Spearman correlation coefficient of 0.65). These data mainly reveal an immune beneficial environment in low-grade ovarian cancer in contrast to high-grade serous ovarian cancer, where immune suppression is not altered by neoadjuvant therapy.

BackgroundThe behavior of the immune system as a driver in the progression of ovarian cancer has barely been studied. Our knowledge is mainly limited to the intra-tumoral adaptive immune system. Because of the widespread metastases of ovarian cancer, an assessment of the circulating immune system seems more accurate.To demonstrate the presence of immune cells in blood samples of patients with ovarian neoplasms.MethodsIn this exploratory prospective cohort study, peripheral blood mononuclear cells were collected at diagnosis from 143 women, including 62 patients with benign cysts, 13 with borderline tumor, 41 with invasive ovarian cancer, and 27 age-matched healthy controls. Immune profile analyses, based on the presence of CD4 (cluster of differentiation), CD8, natural killer cells, myeloid-derived suppressor cells, and regulatory T cells, were performed by fluorescence activated cell sorting.ResultsIn a multivariable analysis, six immune cells (activated regulatory T cells, natural killer cells, myeloid-derived suppressor cells, monocytic myeloid-derived suppressor cells, exhausted monocytic myeloid-derived suppressor cells, and total myeloid cells) were selected as independent predictors of malignancy, with an optimism-corrected area under the receiver operating characteristic curve (AUC) of 0.858. In contrast, a profile based on CD8 and regulatory T cells, the current standard in ovarian cancer immunology, resulted in an AUC of 0.639.ConclusionsOur immune profile in blood suggests an involvement of innate immunosuppression driven by myeloid-derived suppressor cells in the development of ovarian cancer. This finding could contribute to clinical management of patients and in selection of immunotherapy.

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