Targeting EZH2 Reprograms Intratumoral Regulatory T Cells to Enhance Cancer Immunity.

Regulatory T cells (Tregs) are critical for maintaining immune homeostasis, but their presence in tumor tissues impairs anti-tumor immunity and portends poor prognoses in cancer patients. Here, we reveal a mechanism to selectively target and reprogram the function of tumor-infiltrating Tregs (TI-Tregs) by exploiting their dependency on the histone H3K27 methyltransferase enhancer of zeste homolog 2 (EZH2) in tumors. Disruption of EZH2 activity in Tregs, either pharmacologically or genetically, drove the acquisition of pro-inflammatory functions in TI-Tregs, remodeling the tumor microenvironment and enhancing the recruitment and function of CD8+ and CD4+ effector T cells that eliminate tumors. Moreover, abolishing EZH2 function in Tregs was mechanistically distinct from, more potent than, and less toxic than a generalized Treg depletion approach. This study reveals a strategy to target Tregs in cancer that mitigates autoimmunity by reprogramming their function in tumors to enhance anti-cancer immunity

The autoimmune targets in IPEX are dominated by gut epithelial proteins

Non peer reviewe

Markerless Vision-Based Augmented Reality for Urban Planning

Augmented Reality (AR) is a rapidly developing field with numerous potential applications. For example, building developers, public authorities, and other construction industry stakeholders need to visually assess potential new developments with regard to aesthetics, health and safety, and other criteria. Current state-of-the-art visualization technologies are mainly fully virtual, while AR has the potential to enhance those visualizations by observing proposed designs directly within the real environment. A novel AR system is presented, that is most appropriate for urban applications. It is based on monocular vision, is markerless, and does not rely on beacon-based localization technologies (like GPS) or inertial sensors. Additionally, the system automatically calculates occlusions of the built environment on the augmenting virtual objects. Three datasets from real environments presenting different levels of complexity (geometrical complexity, textures, occlusions) are used to demonstrate the performance of the proposed system. Videos augmented with our system are shown to provide realistic and valuable visualizations of proposed changes of the urban environment. Limitations are also discussed with suggestions for future work. © 2012 Computer-Aided Civil and Infrastructure Engineering.Carozza L., Tingdahl D., Bosché F., Van Gool L., ''Markerless vision-based augmented reality for urban planning'', Computer-aided civil and infrastructure engineering, vol. 29, no. 1, pp. 2-17, 2014.status: publishe

Immunological response after WT1 mRNA-loaded dendritic cell immunotherapy in ovarian carcinoma and carcinosarcoma

Background: Dendritic cell (DC)-based immunotherapy is an emerging new treatment option in ovarian cancer, an important cause of cancer-related mortality. Patients and Methods: One patient with ovarian carcinosarcoma (OCS) and one with serous ovarian cancer (SOC) received four weekly vaccinations of autologous DCs electroporated with mRNA coding for the Wilms' tumor gene 1 (WT1). Safety, feasibility and immunogenicity were assessed. Results: Vaccination was feasible without toxicity. In an ex vivo antigen re-stimulation assay of peripheral blood mononuclear cells, both patients showed increasing cluster of differentiation 137 (CD137+) antigen-specific T-cells and interleukin 10 (IL-10) production post-vaccination. Moreover, interleukin-2 (IL-2) production increased (OCS) as well as interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) (SOC). Disease in patients progressed after four vaccines and patients continued with conventional therapies. After cessation of immunotherapy, they had an extended survival of 19 (OCS) and 12 (SOC) months. Conclusion: To our knowledge, we report for the first time the feasibility and T-cell immunogenicity of WT1 mRNA-loaded DC immunotherapy in ovarian cance

Wilms' tumor gene 1 (WT1) - loaded dendritic cell immunotherapy in patients with uterine tumors : a phase I/II clinical trial

Aim: Treatment options are limited in uterine cancer, leading to a poor prognosis. Overexpression of Wilms' tumor gene 1 (WT1), the highest ranked tumor antigen, is attractive for immunotherapy. Patients and Methods: Six pre-treated patients with uterine cancer received four weekly vaccines of autologous dendritic cells (DCs) electroporated with WT1 mRNA. Safety, feasibility and immunogenicity were assessed. In cases of response, patients received monthly booster vaccines. Results: The technique was feasible. One patient had a local allergic reaction. Three out of four Human Leucocyte Antigen-A2 (HLA-A2)-positive patients showed an oncological response; an enrichment of WT1-specific T-cells was observed in two of them. Two HLA-A2-negative patients did not show an oncological or an immunological response. Conclusion: A first series of six patients with uterine cancer treated with WT1 mRNA-electroporated DCs is presented herein. Oncological and immunological responses were observed and are supportive for further researc

Targeting EZH2 Reprograms Intratumoral Regulatory T Cells to Enhance Cancer Immunity.

Regulatory T cells (Tregs) are critical for maintaining immune homeostasis, but their presence in tumor tissues impairs anti-tumor immunity and portends poor prognoses in cancer patients. Here, we reveal a mechanism to selectively target and reprogram the function of tumor-infiltrating Tregs (TI-Tregs) by exploiting their dependency on the histone H3K27 methyltransferase enhancer of zeste homolog 2 (EZH2) in tumors. Disruption of EZH2 activity in Tregs, either pharmacologically or genetically, drove the acquisition of pro-inflammatory functions in TI-Tregs, remodeling the tumor microenvironment and enhancing the recruitment and function of CD8+ and CD4+ effector T cells that eliminate tumors. Moreover, abolishing EZH2 function in Tregs was mechanistically distinct from, more potent than, and less toxic than a generalized Treg depletion approach. This study reveals a strategy to target Tregs in cancer that mitigates autoimmunity by reprogramming their function in tumors to enhance anti-cancer immunity

The 2005 PASCAL visual object classes challenge

Abstract. The PASCAL Visual Object Classes Challenge ran from February to March 2005. The goal of the challenge was to recognize objects from a number of visual object classes in realistic scenes (i.e. not pre-segmented objects). Four object classes were selected: motorbikes, bicycles, cars and people. Twelve teams entered the challenge. In this chapter we provide details of the datasets, algorithms used by the teams, evaluation criteria, and results achieved.

L1CAM expression in endometrial carcinomas: an ENITEC collaboration study

BACKGROUND: Identification of aggressive endometrioid endometrial carcinomas (EECs) and non-endometrioid carcinomas (NEECs) is essential to improve outcome. L1 cell adhesion molecule (L1CAM) expression is a strong prognostic marker in stage I EECs, but less is known about L1CAM expression in advanced-stage EECs and NEECs. This study analyses L1CAM expression in a clinically representative cohort of endometrial carcinomas. METHODS: The expression of L1CAM was immunohistochemically determined in 1199 endometrial carcinomas, treated at one of the European Network for Individualized Treatment of Endometrial Cancer (ENITEC) centres. Staining was considered positive when >10% of the tumour cells expressed L1CAM. The association between L1CAM expression and several clincopathological characteristics and disease outcome was calculated. RESULTS: In all, L1CAM was expressed in 10% of the 935 stage I EECs, 18% of the 160 advanced stage EECs, and 75% of the 104 NEECs. The expression of L1CAM was associated with advanced stage, nodal involvement, high tumour grade, non-endometrioid histology, lymphovascular space invasion, and distant recurrences in all cases, and with reduced survival in the EECs, but not in the NEECs. CONCLUSIONS: The expression of L1CAM is a strong predictor of poor outcome in EECs, but not NEECs. It is strongly associated with non-endometrioid histology and distant spread, and could improve the postoperative selection of high-risk endometrial carcinomas. The value of L1CAM expression in the preoperative selection of high-risk endometrial carcinomas should be studie