MHC-I and PD-L1 Expression is Associated with Decreased Tumor Outgrowth and is Radiotherapy-inducible in the Murine Head and Neck Squamous Cell Carcinoma Model MOC1.

Introduction: Combined radiotherapy and immune checkpoint inhibition is a potential treatment option for head and neck squamous cell carcinoma (HNSCC). Immunocompetent mouse models can help to successfully develop radio- immunotherapy combinations and to increase our understanding of the effects of radiotherapy on the tumor microenvironment for future clinical translation. Therefore, the aim of this study was to develop a homogeneous, reproducible HNSCC model originating from the Mouse Oral Cancer 1 (MOC1) HNSCC cell line, and to explore the radiotherapy-induced changes in its tumor microenvironment, using flow cytometry and PD-L1 microSPECT/CT imaging.

Mechanical high-intensity focused ultrasound creates unique tumor debris enhancing dendritic cell-induced T cell activation.

Introduction: tumor ablation releases a unique repertoire of antigens from a heterogeneous population of tumor cells. High-intensity focused ultrasound (HIFU) is a completely noninvasive ablation therapy that can be used to ablate tumors either by heating (thermal (T)-HIFU) or by mechanical disruption (mechanical (M)-HIFU). How different HIFU ablation techniques compare with respect to their antigen release profile, their activation of responder T cells, and their ability to synergize with immune stimuli remains to be elucidated.

NSAIDs affect dendritic cell cytokine production.

Background: Immunotherapy is now considered as the new pillar in treatment of cancer patients. Dendritic cells (DCs) play an essential role in stimulating anti-tumor immune responses, as they are capable of cross-presenting exogenous tumor antigens in MHCI complexes to activate naïve CD8+ T cells. Analgesics, like non-steroid anti-inflammatory drugs (NSAIDs), are frequently given to cancer patients to help relieve pain, however little is known about their impact on DC function.

Immune Modulation Plus Tumor Ablation: Adjuvants and Antibodies to Prime and Boost Anti-Tumor Immunity .

tumor ablation techniques, like radiotherapy, cryo- and heat-based thermal ablation are successfully applied in oncology for local destruction of tumor masses. Although diverse in technology and mechanism of inducing cell death, ablative techniques share one key feature: they generate tumor debris which remains . This tumor debris functions as an unbiased source of tumor antigens available to the immune system and has led to the concept of cancer vaccination.

Anti-GD2 antibody and Vorinostat immunocombination therapy is highly effective in an aggressive orthotopic neuroblastoma model.

Neuroblastoma is a childhood malignancy and in the majority of patients, the primary tumor arises in one of the adrenal glands. Neuroblastoma cells highly express the disialoganglioside GD2, which is the primary target for the development of neuroblastoma immunotherapy. Anti-GD2 mAbs have shown clinical efficacy and are integrated into standard treatment for high-risk neuroblastoma patients.

LGR5 in breast cancer and ductal carcinoma in situ: a diagnostic and prognostic biomarker and a therapeutic target.

Background: Novel biomarkers are required to discern between breast tumors that should be targeted for treatment from those that would never become clinically apparent and/or life threatening for patients. Moreover, therapeutics that specifically target breast cancer (BC) cells with tumor-initiating capacity to prevent recurrence are an unmet need. We investigated the clinical importance of LGR5 in BC and ductal carcinoma in situ (DCIS) to explore LGR5 as a biomarker and a therapeutic target.

Tumor ablation plus co-administration of CpG and saponin adjuvants affects IL-1 production and multifunctional T cell numbers in tumor draining lymph nodes.

Background: Tumor ablation techniques, like cryoablation, are successfully used in the clinic to treat tumors. The tumor debris remaining in situ after ablation is a major antigen depot, including neoantigens, which are presented by dendritic cells (DCs) in the draining lymph nodes to induce tumor-specific CD8 T cells. We have previously shown that co-administration of adjuvants is essential to evoke strong in vivo antitumor immunity and the induction of long-term memory.

DC-SCRIPT affects mammary organoids branching morphogenesis by modulating the FGFR1-pERK signaling axis.

Loss of expression of the transcription regulator DC-SCRIPT (Zfp366) is a prominent prognostic event in estrogen receptor-positive breast cancer patients. Studying the inherent link between breast morphogenesis and tumorigenesis, we recently reported that DC-SCRIPT affects normal mammary branching morphogenesis and mammary epithelium homeostasis. Here we investigated the molecular mechanism involved in DC-SCRIPT mediated regulation of FGF2 induced mammary branching morphogenesis in a 3D organoid culture system.

DC-SCRIPT deficiency delays mouse mammary gland development and branching morphogenesis.

Mammary glands are unique organs in which major adaptive changes occur in morphogenesis and development after birth. Breast cancer is the most common cancer and a major cause of mortality in females worldwide. We have previously identified the loss of expression of the transcription regulator DC-SCRIPT (Zfp366) as a prominent prognostic event in estrogen receptor positive breast cancer patients.

Combined sialic acid and histone deacetylase (HDAC) inhibitor treatment up-regulates the neuroblastoma antigen GD2.

Neuroblastoma cells highly express the disialoganglioside GD2, a tumor-associated carbohydrate antigen, which is only sparsely expressed on healthy tissue. GD2 is a primary target for the development of immunotherapy for neuroblastoma. Immunotherapy with monoclonal anti-GD2 antibodies has proven safety and efficacy in clinical trials and is included in the standard treatment for children with high-risk neuroblastoma.

Cancer Immunotherapy Getting Brainy: Visualizing the Distinctive CNS Metastatic Niche to Illuminate Therapeutic Resistance.

The advent of cancer immunotherapy (CIT) and its success in treating primary and metastatic cancer may offer substantially improved outcomes for patients. Despite recent advancements, many malignancies remain resistant to CIT, among which are brain metastases, a particularly virulent disease with no apparent cure. The immunologically unique niche of the brain has prompted compelling new questions in immuno-oncology such as the effects of tissue-specific differences in immune response, heterogeneity between primary tumors and distant metastases, and the role of spatiotemporal dynamics in shaping an effective anti-tumor immune response.

Impact of MR-guided boiling histotripsy in distinct murine tumor models.

Interest in mechanical high intensity focused ultrasound (HIFU) ablation is rapidly growing. Boiling histotripsy (BH) is applied for mechanical fragmentation of soft tissue into submicron fragments with limited temperature increase using the shock wave and cavitation effects of HIFU. Research on BH has been largely limited to ex vivo experiments.

Thermal and mechanical high-intensity focused ultrasound: perspectives on tumor ablation, immune effects and combination strategies.

Tumor ablation technologies, such as radiofrequency-, cryo- or high-intensity focused ultrasound (HIFU) ablation will destroy tumor tissue in a minimally invasive manner. Ablation generates large volumes of tumor debris in situ, releasing multiple bio-molecules like tumor antigens and damage-associated molecular patterns. To initiate an adaptive antitumor immune response, antigen-presenting cells need to take up tumor antigens and, following activation, present them to immune effector cells.

Ex vivo Live Imaging of Lung Metastasis and Their Microenvironment.

Metastasis is a major cause for cancer-related morbidity and mortality. Metastasis is a multistep process and due to its complexity, the exact cellular and molecular processes that govern metastatic dissemination and growth are still elusive. Live imaging allows visualization of the dynamic and spatial interactions of cells and their microenvironment.

Adaptive Immune Regulation of Mammary Postnatal Organogenesis.

Postnatal organogenesis occurs in an immune competent environment and is tightly controlled by interplay between positive and negative regulators. Innate immune cells have beneficial roles in postnatal tissue remodeling, but roles for the adaptive immune system are currently unexplored. Here we show that adaptive immune responses participate in the normal postnatal development of a non-lymphoid epithelial tissue.