Search results for "immunotherapy"
showing 10 items of 830 documents
Characterizing diversity in the tumor-immune microenvironment of distinct subclasses of gastroesophageal adenocarcinomas
2020
Background Gastroesophageal adenocarcinomas (GEAs) are heterogeneous cancers where immune checkpoint inhibitors have robust efficacy in heavily inflamed microsatellite instability (MSI) or Epstein-Barr virus (EBV)-positive subtypes. Immune checkpoint inhibitor responses are markedly lower in diffuse/genome stable (GS) and chromosomal instable (CIN) GEAs. In contrast to EBV and MSI subtypes, the tumor microenvironment of CIN and GS GEAs have not been fully characterized to date, which limits our ability to improve immunotherapeutic strategies. Patients and methods Here we aimed to identify tumor-immune cell association across GEA subclasses using data from The Cancer Genome Atlas (N = 453 GE…
Combined Analysis of Antigen Presentation and T-cell Recognition Reveals Restricted Immune Responses in Melanoma.
2018
Abstract The quest for tumor-associated antigens (TAA) and neoantigens is a major focus of cancer immunotherapy. Here, we combine a neoantigen prediction pipeline and human leukocyte antigen (HLA) peptidomics to identify TAAs and neoantigens in 16 tumors derived from seven patients with melanoma and characterize their interactions with their tumor-infiltrating lymphocytes (TIL). Our investigation of the antigenic and T-cell landscapes encompassing the TAA and neoantigen signatures, their immune reactivity, and their corresponding T-cell identities provides the first comprehensive analysis of cancer cell T-cell cosignatures, allowing us to discover remarkable antigenic and TIL similarities b…
Novel Opportunities for Cathepsin S Inhibitors in Cancer Immunotherapy by Nanocarrier-Mediated Delivery
2020
Cathepsin S (CatS) is a secreted cysteine protease that cleaves certain extracellular matrix proteins, regulates antigen presentation in antigen-presenting cells (APC), and promotes M2-type macrophage and dendritic cell polarization. CatS is overexpressed in many solid cancers, and overall, it appears to promote an immune-suppressive and tumor-promoting microenvironment. While most data suggest that CatS inhibition or knockdown promotes anti-cancer immunity, cell-specific inhibition, especially in myeloid cells, appears to be important for therapeutic efficacy. This makes the design of CatS selective inhibitors and their targeting to tumor-associated M2-type macrophages (TAM) and DC an attr…
Targeting Neoepitopes to Treat Solid Malignancies: Immunosurgery
2020
Successful outcome of immune checkpoint blockade in patients with solid cancers is in part associated with a high tumor mutational burden (TMB) and the recognition of private neoantigens by T-cells. The quality and quantity of target recognition is determined by the repertoire of ‘neoepitope’-specific T-cell receptors (TCRs) in tumor-infiltrating lymphocytes (TIL), or peripheral T-cells. Interferon gamma (IFN-γ), produced by T-cells and other immune cells, is essential for controlling proliferation of transformed cells, induction of apoptosis and enhancing human leukocyte antigen (HLA) expression, thereby increasing immunogenicity of cancer cells. TCR αβ-dependent therapies should account f…
Utilizing the nanosecond pulse technique to improve antigen intracellular delivery and presentation to treat tongue squamous cell carcinoma
2017
Background Tongue squamous cell carcinoma is the most common squamous cell carcinoma of the head and neck. Immunotherapy has great potential in the treatment of tongue squamous cell carcinoma because of its unique advantages. However, the efficacy of immunotherapy is limited by the efficiency of antigen phagocytosis by immune cells. Material and Methods We extracted dendritic cells (DCs) from human peripheral blood. Utilizing a nanosecond pulsed electric field (nsPEF), we deliver the tumour lysate protein into DCs and then incubate the DCs with PBMCs to obtain specific T cells to kill tumour cells. The biosafety of nsPEF was evaluated by the ANNEXIN V-FITC/PI kit. The efficacy of lysate pro…
Targeting myeloid cells in the tumor sustaining microenvironment.
2017
Myeloid cells are the most abundant cells in the tumor microenvironment (TME). The tumor recruits and modulates endogenous myeloid cells to tumor-associated macrophages (TAM), dendritic cells (DC), myeloid-derived suppressor cells (MDSC) and neutrophils (TAN), to sustain an immunosuppressive environment. Pathologically overexpressed mediators produced by cancer cells like granulocyte-macrophage colony-stimulating- and vascular endothelial growth factor induce myelopoiesis in the bone marrow. Excess of myeloid cells in the blood, periphery and tumor has been associated with tumor burden. In cancer, myeloid cells are kept at an immature state of differentiation to be diverted to an immunosupp…
Una visión integral del cáncer (II). Campos de estudio y biomarcadores emergentes
2019
Pathology and clinical oncology work hand in hand so that techniques and treatments, biomarkers and antibodies share the common goal of identifying integral new treatment regimens that are more effective and less aggressive. Evidence shows how tissue mechanics affect carcinogenesis and that tumor heterogeneity depends on metabolic stromal alteration and the Warburg effect of malignant cells, regulated directly by PD-1, becoming a target for immunotherapy. Proliferation and apoptosis depend on mitochondrial dysfunction in tumor cells, determining the grade of chemo/radio-resistance. The status of intestinal microbiota regulates immune response, tumor microenvironment structure and oncologic …
Les lymphocytes Th9
2016
Th9 cells are CD4 T helper cells characterized by their ability to produce IL-9 and IL-21. These cells are obtained from naive CD4(+) T cells cultured in the presence of TGF-β and IL-4. Thus their differentiation results from the balance between the signaling pathways induced by IL-4 in one hand and the one induced by TGF-β in the other hand. These cells are inflammatory cells and were first described in the context of atopic and autoimmune diseases in which they have a pathogenic role. They are also involved in the defense against parasite infections. Recently, some reports defined Th9 anticancer properties through their cytokine secretion. Indeed, their high secretion of IL-9 and IL-21 in…
Cytomegalovirus vector expressing RAE-1γ induces enhanced anti-tumor capacity of murine CD8+ T cells
2017
Designing of CD8 T cell vaccines which would provide protection against tumors is still considered a great challenge in immunotherapy. Here we show a robust potential of a cytomegalovirus (CMV) vector expressing the NKG2D ligand RAE-1γ as CD8 T cell-based vaccine against malignant tumors. Immunization with the CMV vector expressing RAE-1γ delayed tumor growth or even provided complete protection against tumor challenge in both prophylactic and therapeutic settings. Moreover, a potent tumor control in mice vaccinated with this vector can be further enhanced by blocking the immune checkpoints TIGIT and PD-1. Expression of RAE-1γ by the CMV vector potentiated expansion of KLRG1+ CD8 T cells wi…
mRNA: A Versatile Molecule for Cancer Vaccines
2016
mRNA vaccines are finally ready to assume their rightful place at the forefront of nucleic acid- based vaccines. Major achievements within the last two decades have turned this highly versatile molecule into a safe and very attractive pharmaceutical platform that combines many positive attributes able to address a broad range of diseases, including cancer. The simplicity of mRNA vaccines greatly reduces complications generally associated with the production of biological vaccines. Intrinsic costimulatory and inflammatory triggers in addition to the provision of the antigenic information makes mRNA an all- in-one molecule that does not need additional adjuvants and that does not pose the ris…