Small-Molecule Natural Product Physachenolide C Potentiates Immunotherapy Efficacy by Targeting BET Proteins.

Screening for sensitizers of cancer cells to TRAIL-mediated apoptosis identified a natural product of the 17β-hydroxywithanolide (17-BHW) class, physachenolide C (PCC), as a promising hit. In this study, we show that PCC was also able to sensitize melanoma and renal carcinoma cells to apoptosis in response not only to TRAIL, but also to the synthetic polynucleotide poly I:C, a viral mimetic and immune activator, by reducing levels of antiapoptotic proteins cFLIP and Livin. Both death receptor and TLR3 signaling elicited subsequent increased assembly of a proapoptotic ripoptosome signaling complex.

Bortezomib Sustains T Cell Function by Inducing miR-155-Mediated Downregulation of SOCS1 and SHIP1.

Suppressive mechanisms operating within T cells are linked to immune dysfunction in the tumor microenvironment. We have previously reported using adoptive T cell immunotherapy models that tumor-bearing mice treated with a regimen of proteasome inhibitor, bortezomib - a dipeptidyl boronate, show increased antitumor lymphocyte effector function and survival. Here, we identify a mechanism for the improved antitumor CD8 T cell function following bortezomib treatment.

Critical Neurotransmitters in the Neuroimmune Network.

Immune cells rely on cell-cell communication to specify and fine-tune their responses. They express an extensive network of cell communication modes, including a vast repertoire of cell surface and transmembrane receptors and ligands, membrane vesicles, junctions, ligand and voltage-gated ion channels, and transporters. During a crosstalk between the nervous system and the immune system these modes of cellular communication and the downstream signal transduction events are influenced by neurotransmitters present in the local tissue environments in an autocrine or paracrine fashion.

Phase II Study of Immunotherapy With Tecemotide and Bevacizumab After Chemoradiation in Patients With Unresectable Stage III Non-Squamous Non-Small-Cell Lung Cancer (NS-NSCLC): A Trial of the ECOG-ACRIN Cancer Research Group (E6508).

Introduction: Although chemoradiotherapy (CRT) is the standard of care for patients with unresectable stage III non-small-cell lung cancer (LA-NSCLC), most patients relapse. Tecemotide is a MUC1 antigen-specific cancer immunotherapy vaccine. Bevacizumab improves survival in advanced nonsquamous (NS)-NSCLC and has a role in immune modulation.

Correction to: Determinant roles of dendritic cell-expressed Notch Delta-like and Jagged ligands on anti-tumor T-cell immunity.

Following publication of the original article [1], the author reported the wrong version of Figs. 5 and 7 have been published. The correct version of the figures can be found below.

Determinant roles of dendritic cell-expressed Notch Delta-like and Jagged ligands on anti-tumor T cell immunity.

Background: Notch intercellular communication instructs tissue-specific T-cell development and function. In this study, we explored the roles of dendritic cell (DC)-expressed Notch ligands in the regulation of T-cell effector function.

Methods: We generated mice with CD11c lineage-specific deletion of Notch Delta-like ligand (Dll)1 and Jagged (Jag)2.

Challenges and future perspectives of T cell immunotherapy in cancer.

Since the formulation of the tumour immunosurveillance theory, considerable focus has been on enhancing the effectiveness of host antitumour immunity, particularly with respect to T cells. A cancer evades or alters the host immune response by various ways to ensure its development and survival. These include modifications of the immune cell metabolism and T cell signalling.

IL-27 limits central nervous system viral clearance by promoting IL-10 and enhances demyelination.

IL-27 is a pleiotropic member of the IL-6 and IL-12 cytokine family composed of the IL-27p28 and the EBV-induced gene 3. IL-27 and its receptor mRNA are both upregulated in the CNS during acute encephalomyelitis induced by the JHM strain of mouse hepatitis virus (JHMV) and sustained during viral persistence. Contributions of IL-27 to viral pathogenesis were evaluated by infection of IL-27Rα-chain-deficient (IL-27Rα(-/-)) mice.

Role of CD25(+) CD4(+) T cells in acute and persistent coronavirus infection of the central nervous system.

The influence of CD25(+)CD4(+) regulatory T cells (Treg) on acute and chronic viral infection of the central nervous system (CNS) was examined using a glial tropic murine coronavirus. Treg in the CNS were highest during initial T cell mediated virus control, decreased and then remained relatively stable during persistence. Anti-CD25 treatment did not affect CNS recruitment of inflammatory cells.

Influence of the CCR-5/MIP-1 α axis in the pathogenesis of Rocio virus encephalitis in a mouse model.

Rocio virus (ROCV) caused an outbreak of human encephalitis during the 1970s in Brazil and its immunopathogenesis remains poorly understood. CC-chemokine receptor 5 (CCR5) is a chemokine receptor that binds to macrophage inflammatory protein (MIP-1 α). Both molecules are associated with inflammatory cells migration during infections.

A DNA vaccine candidate encoding the structural prM/E proteins elicits a strong immune response and protects mice against dengue-4 virus infection.

A DNA vaccine expressing dengue-4 virus premembrane (prM) and envelope (E) genes was produced by inserting these genes into a mammalian expression plasmid (pCI). Following a thorough screening, including confirmation of protein expression in vitro, a recombinant clone expressing these genes was selected and used to immunize BALB/c mice. After 3 immunizations all the animals produced detectable levels of neutralizing antibodies against dengue-4 virus.