Search results for "T Cell"
showing 10 items of 2228 documents
LC3-Associated Phagocytosis (LAP): A Potentially Influential Mediator of Efferocytosis-Related Tumor Progression and Aggressiveness
2020
One aim of cancer therapies is to induce apoptosis of tumor cells. Efficient removal of the apoptotic cells requires coordinated efforts between the processes of efferocytosis and LC3-associated phagocytosis (LAP). However, this activity has also been shown to produce anti-inflammatory and immunosuppressive signals that can be utilized by live tumor cells to evade immune defense mechanisms, resulting in tumor progression and aggressiveness. In the absence of LAP, mice exhibit suppressed tumor growth during efferocytosis, while LAP-sufficient mice show enhanced tumor progression. Little is known about how LAP or its regulators directly affect efferocytosis, tumor growth and treatment respons…
The secreted protein acidic and rich in cysteine is a critical mediator of cell death program induced by WIN/TRAIL combined treatment in osteosarcoma…
2015
Abstract Secreted protein acidic and rich in cysteine (SPARC) is a multi-functional protein which modulates cell-cell and cell-matrix interactions. In cancer cells, SPARC behaves as a tumor promoter in a number of tumors, but it can also act as a tumor suppressor factor. Our previous results showed that the synthetic cannabinoid WIN55,212-2 (WIN), a potent cannabinoid receptor agonist, is able to sensitize osteosarcoma MG63 cells to TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis which is accompanied with endoplasmic reticulum (ER)-stress induction and the increase in autophagic markers. In the present investigation, we studied the role of SPARC in WIN/TRAIL-induced apoptosi…
Rational Combination of Parvovirus H1 With CTLA-4 and PD-1 Checkpoint Inhibitors Dampens the Tumor Induced Immune Silencing
2019
The recent therapeutic success of immune checkpoint inhibitors in the treatment of advanced melanoma highlights the potential of cancer immunotherapy. Oncolytic virus-based therapies may further improve the outcome of these cancer patients. A human ex vivo melanoma model was used to investigate the oncolytic parvovirus H-1 (H-1PV) in combination with ipilimumab and/or nivolumab. The effect of this combination on activation of human T lymphocytes was demonstrated. Expression of CTLA-4, PD-1, and PD-L1 immune checkpoint proteins was upregulated in H-1PV-infected melanoma cells. Nevertheless, maturation of antigen presenting cells such as dendritic cells was triggered by H-1PV infected melanom…
Primary and metastatic brain cancer genomics and emerging biomarkers for immunomodulatory cancer treatment
2018
Abstract: Recent studies with immunomodulatory agents targeting both cytotoxic T-lymphocyte protein 4 (CTLA4) and programmed cell death 1 (PD1)/programmed cell death ligand 1 (PDL1) have shown to be very effective in several cancers revealing an unexpected great activity in patients with both primary and metastatic brain tumors. Combining anti-CTLA4 and anti-PD1 agents as upfront systemic therapy has revealed to further increase the clinical benefit observed with single agent, even at cost of higher toxicity. Since the brain is an immunological specialized area it's crucial to establish the specific composition of the brain tumors' micro environment in order to predict the potential activit…
Melanoma Lesions Independently Acquire T-cell Resistance during Metastatic Latency
2016
Abstract Melanoma often recurs after a latency period of several years, presenting a T cell–edited phenotype that reflects a role for CD8+ T cells in maintaining metastatic latency. Here, we report an investigation of a patient with multiple recurrent lesions, where poorly immunogenic melanoma phenotypes were found to evolve in the presence of autologous tumor antigen–specific CD8+ T cells. Melanoma cells from two of three late recurrent metastases, developing within a 6-year latency period, lacked HLA class I expression. CD8+ T cell–resistant, HLA class I–negative tumor cells became clinically apparent 1.5 and 6 years into stage IV disease. Genome profiling by SNP arrays revealed that HLA …
Cancer Acidity and Hypertonicity Contribute to Dysfunction of Tumor-Associated Dendritic Cells: Potential Impact on Antigen Cross-Presentation Machin…
2020
Macrophages (M) and dendritic cells (DC), major players of the mononuclear phagocyte system (MoPh), are potent antigen presenting cells that steadily sense and respond to signals from the surrounding microenvironment, leading to either immunogenic or tolerogenic outcomes. Next to classical MHC-I/MHC-II antigen-presentation pathways described in the vast majority of cell types, a subset of MoPh (CD8+, XCR1+, CLEC9A+, BDCA3+ conventional DCs in human) is endowed with a high competence to cross-present external (engulfed) antigens on MHC-I molecules to CD8+ T-cells. This exceptional DC function is thought to be a crucial crossroad in cytotoxic antitumor immunity and has been extensively studie…
Vγ9Vδ2 T Cells as Strategic Weapons to Improve the Potency of Immune Checkpoint Blockade and Immune Interventions in Human Myeloma
2018
The advent of immune checkpoint (ICP) blockade has introduced an unprecedented paradigm shift in the treatment of cancer. Though very promising, there is still a substantial proportion of patients who do not respond or develop resistance to ICP blockade. In vitro and in vivo models are eagerly needed to identify mechanisms to maximize the immune potency of ICP blockade and overcome primary and acquired resistance to ICP blockade. Vγ9Vδ2 T cells isolated from the bone marrow (BM) from multiple myeloma (MM) are excellent tools to investigate the mechanisms of resistance to PD-1 blockade and to decipher the network of mutual interactions between PD-1 and the immune suppressive tumor microenvir…
The Functional Crosstalk between Myeloid-Derived Suppressor Cells and Regulatory T Cells within the Immunosuppressive Tumor Microenvironment
2021
Simple Summary Immunotherapy improved the therapeutic landscape for patients with advanced cancer diseases. However, many patients do not benefit from immunotherapy. The bidirectional crosstalk between myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg) contributes to immune evasion, limiting the success of immunotherapy by checkpoint inhibitors. This review aims to outline the current knowledge of the role and the immunosuppressive properties of MDSC and Treg within the tumor microenvironment (TME). Furthermore, we will discuss the importance of the functional crosstalk between MDSC and Treg for immunosuppression, issuing particularly the role of cell adhesion molecules. …
Platelet-Derived GARP Induces Peripheral Regulatory T Cells—Potential Impact on T Cell Suppression in Patients with Melanoma-Associated Thrombocytosis
2020
Platelets have been recently described as an important component of the innate and adaptive immunity through their interaction with immune cells. However, information on the platelet&ndash
Adapter Chimeric Antigen Receptor (AdCAR)-Engineered NK-92 Cells for the Multiplex Targeting of Bone Metastases
2021
Simple Summary Metastatic disease remains one of the biggest challenges for tumor therapy. The aim of our study was the preclinical evaluation of adapter chimeric antigen receptor (AdCAR)-engineered NK-92 cell efficacy as a possible treatment strategy for various types of bone metastatic cancers. We confirmed that AdCAR NK-92 cells successfully induces tumor cell lysis in bone metastasis cell lines derived from mammary, renal cell and colorectal carcinoma as well as melanoma in a specific and controllable manner, thus, establishing a potent cellular product with universal applicability and quick clinical translation potential for the treatment of solid tumors, including metastases. Abstract…