Comparing neoantigen cancer vaccines and immune checkpoint therapy unveils an effective vaccine and anti-TREM2 macrophage-targeting dual therapy.

The goal of therapeutic cancer vaccines and immune checkpoint therapy (ICT) is to promote T cells with anti-tumor capabilities. Here, we compared mutant neoantigen (neoAg) peptide-based vaccines with ICT in preclinical models. NeoAg vaccines induce the most robust expansion of proliferating and stem-like PD-1TCF-1 neoAg-specific CD8 T cells in tumors.

Elucidating immune-related gene transcriptional programs via factorization of large-scale RNA-profiles.

Recent developments in immunotherapy, including immune checkpoint blockade (ICB) and adoptive cell therapy (ACT), have encountered challenges such as immune-related adverse events and resistance, especially in solid tumors. To advance the field, a deeper understanding of the molecular mechanisms behind treatment responses and resistance is essential. However, the lack of functionally characterized immune-related gene sets has limited data-driven immunological research.

Elucidating immune-related gene transcriptional programs via factorization of large-scale RNA-profiles.

Recent developments in immunotherapy, including immune checkpoint blockade (ICB) and adoptive cell therapy, have encountered challenges such as immune-related adverse events and resistance, especially in solid tumors. To advance the field, a deeper understanding of the molecular mechanisms behind treatment responses and resistance is essential. However, the lack of functionally characterized immune-related gene sets has limited data-driven immunological research.

Induction of complementary immunogenic necroptosis and apoptosis cell death pathways inhibits cancer metastasis and relapse.

Interactions of light-sensitive drugs and materials with Cerenkov radiation-emitting radiopharmaceuticals generate cytotoxic reactive oxygen species (ROS) to inhibit localized and disseminated cancer progression, but the cell death mechanisms underlying this radionuclide stimulated dynamic therapy (RaST) remain elusive. Using ROS-regenerative nanophotosensitizers coated with a tumor-targeting transferrin-titanocene complex (TiO-TC-Tf) and radiolabeled 2-fluorodeoxyglucose (FDG), we found that adherent dying cells maintained metabolic activity with increased membrane permeabilization. Mechanistic assessment of these cells revealed that RaST activated the expression of RIPK-1 and RIPK-3, which mediate necroptosis cell death.

Neoantigen Cancer Vaccines and Different Immune Checkpoint Therapies Each Utilize Both Converging and Distinct Mechanisms that in Combination Enable Synergistic Therapeutic Efficacy.

The goal of therapeutic cancer vaccines and immune checkpoint therapy (ICT) is to eliminate cancer by expanding and/or sustaining T cells with anti-tumor capabilities. However, whether cancer vaccines and ICT enhance anti-tumor immunity by distinct or overlapping mechanisms remains unclear. Here, we compared effective therapeutic tumor-specific mutant neoantigen (NeoAg) cancer vaccines with anti-CTLA-4 and/or anti-PD-1 ICT in preclinical models.

Lasing Effect in Symmetrical van der Waals Heterostructured Metasurfaces Due to Lattice-Induced Multipole Coupling.

New practical ways to reach the lasing effect in symmetrical metasurfaces have been developed and theoretically demonstrated. Our approach is based on excitation of the resonance of an octupole quasi-trapped mode (OQTM) in heterostructured symmetrical metasurfaces composed of monolithic disk-shaped van der Waals meta-atoms featured by thin photoluminescent layers and placed on a substrate. We revealed that the coincidence of the photoluminescence spectrum maximum of these layers with the wavelength of high-quality OQTM resonance leads to the lasing effect.

CD5 expression by dendritic cells directs T cell immunity and sustains immunotherapy responses.

The induction of proinflammatory T cells by dendritic cell (DC) subtypes is critical for antitumor responses and effective immune checkpoint blockade (ICB) therapy. Here, we show that human CD1cCD5 DCs are reduced in melanoma-affected lymph nodes, with CD5 expression on DCs correlating with patient survival. Activating CD5 on DCs enhanced T cell priming and improved survival after ICB therapy.

Intestinal toxicity to CTLA-4 blockade driven by IL-6 and myeloid infiltration.

Immune checkpoint blockade (ICB) has revolutionized cancer treatment, yet quality of life and continuation of therapy can be constrained by immune-related adverse events (irAEs). Limited understanding of irAE mechanisms hampers development of approaches to mitigate their damage. To address this, we examined whether mice gained sensitivity to anti-CTLA-4 (αCTLA-4)-mediated toxicity upon disruption of gut homeostatic immunity.

ATR-mediated CD47 and PD-L1 up-regulation restricts radiotherapy-induced immune priming and abscopal responses in colorectal cancer.

Radiotherapy (RT) of colorectal cancer (CRC) can prime adaptive immunity against tumor-associated antigen (TAA)-expressing CRC cells systemically. However, abscopal tumor remissions are extremely rare, and the postirradiation immune escape mechanisms in CRC remain elusive. Here, we found that irradiated CRC cells used ATR-mediated DNA repair signaling pathway to up-regulate both CD47 and PD-L1, which through engagement of SIRPα and PD-1, respectively, prevented phagocytosis by antigen-presenting cells and thereby limited TAA cross-presentation and innate immune activation.

Cancer Immunoediting in the Era of Immuno-oncology.

Basic science breakthroughs in T-cell biology and immune-tumor cell interactions ushered in a new era of cancer immunotherapy. Twenty years ago, cancer immunoediting was proposed as a framework to understand the dynamic process by which the immune system can both control and shape cancer and in its most complex form occurs through three phases termed elimination, equilibrium, and escape. During cancer progression through these phases, tumors undergo immunoediting, rendering them less immunogenic and more capable of establishing an immunosuppressive microenvironment.

[Results of modified submandibular surgical approach usage for the mouth floor phlegmons treatment with respect to dynamic of local non-specific resistance].

The Aim Of The Study: Was increasing of treatment effectiveness of patients with mouth floor odontogenic phlegmon (MFOP) by modified of surgical approach usage.

Materials And Methods: The prospective controlled, randomized, simple blinded clinical trial, II b level of evidence, comprised 86 patients with MFOP which formed main and control groups. The main group consisted of 40 patients treated with designed «Method for surgical treatment of odontogenic oral phlegmon of mouth floor with partial dissection of sublingual-submandibular sac».

BHLHE40 Regulates the T-Cell Effector Function Required for Tumor Microenvironment Remodeling and Immune Checkpoint Therapy Efficacy.

Immune checkpoint therapy (ICT) using antibody blockade of programmed cell death protein 1 (PD-1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) can provoke T cell-dependent antitumor activity that generates durable clinical responses in some patients. The epigenetic and transcriptional features that T cells require for efficacious ICT remain to be fully elucidated. Herein, we report that anti-PD-1 and anti-CTLA-4 ICT induce upregulation of the transcription factor BHLHE40 in tumor antigen-specific CD8+ and CD4+ T cells and that T cells require BHLHE40 for effective ICT in mice bearing immune-edited tumors.

TREM2 Modulation Remodels the Tumor Myeloid Landscape Enhancing Anti-PD-1 Immunotherapy.

Checkpoint immunotherapy unleashes T cell control of tumors, but is undermined by immunosuppressive myeloid cells. TREM2 is a myeloid receptor that transmits intracellular signals that sustain microglial responses during Alzheimer's disease. TREM2 is also expressed by tumor-infiltrating macrophages.

All-Plasmonic Switching Effect in the Graphene Nanostructures Containing Quantum Emitters.

Nonlinear plasmonic effects in perspective 2D materials containing low-dimensional quantum emitters can be a basis of a novel technological platform for the fabrication of fast all-plasmonic triggers, transistors, and sensors. This article considers the conditions for achieving a strong coupling between the surface plasmon-polariton (SPP) and quantum emitter taking into account the modification of local density of optical states in graphene waveguide. In the condition of strong coupling, nonlinear interaction between two SPP modes propagating along the graphene waveguide integrated with a stub nanoresonator loaded with core-shell semiconductor nanowires (NWs) was investigated.

MHC-II neoantigens shape tumour immunity and response to immunotherapy.

The ability of the immune system to eliminate and shape the immunogenicity of tumours defines the process of cancer immunoediting. Immunotherapies such as those that target immune checkpoint molecules can be used to augment immune-mediated elimination of tumours and have resulted in durable responses in patients with cancer that did not respond to previous treatments. However, only a subset of patients benefit from immunotherapy and more knowledge about what is required for successful treatment is needed.

[Features of hemodynamics in patients with a local form of odontogenic purulent infection and chronic diseases of the cardiovascular system].

The aim of the study was to study hemodynamic parameters in patients with a local form of odontogenic infection (LFOI) in the presence of diseases of the cardiovascular system and without background pathology. 5 groups were formed: group 1 - patients with LFOI without background diseases (49 patients, mean age 29 [25; 37] years); group 2 - healthy individuals (25 people, mean age 24.7±0.

High-Dimensional Analysis Delineates Myeloid and Lymphoid Compartment Remodeling during Successful Immune-Checkpoint Cancer Therapy.

Although current immune-checkpoint therapy (ICT) mainly targets lymphoid cells, it is associated with a broader remodeling of the tumor micro-environment. Here, using complementary forms of high-dimensional profiling, we define differences across all hematopoietic cells from syngeneic mouse tumors during unrestrained tumor growth or effective ICT. Unbiased assessment of gene expression of tumor-infiltrating cells by single-cell RNA sequencing (scRNAseq) and longitudinal assessment of cellular protein expression by mass cytometry (CyTOF) revealed significant remodeling of both the lymphoid and myeloid intratumoral compartments.

Author Correction: Checkpoint blockade immunotherapy reshapes the high-dimensional phenotypic heterogeneity of murine intratumoural neoantigen-specific CD8 T cells.

The original version of this Article omitted a declaration from the competing interests statement, which should have included the following: 'R.D.S.

The RNA-Binding Protein HuR Posttranscriptionally Regulates IL-2 Homeostasis and CD4 Th2 Differentiation.

Posttranscriptional gene regulation by RNA-binding proteins, such as HuR (), fine-tune gene expression in T cells, leading to powerful effects on immune responses. HuR can stabilize target mRNAs and/or promote translation by interacting with their 3' untranslated region adenylate and uridylate-rich elements. It was previously demonstrated that HuR facilitates Th2 cytokine expression by mRNA stabilization.

Checkpoint blockade immunotherapy reshapes the high-dimensional phenotypic heterogeneity of murine intratumoural neoantigen-specific CD8 T cells.

The analysis of neoantigen-specific CD8 T cells in tumour-bearing individuals is challenging due to the small pool of tumour antigen-specific T cells. Here we show that mass cytometry with multiplex combinatorial tetramer staining can identify and characterize neoantigen-specific CD8 T cells in mice bearing T3 methylcholanthrene-induced sarcomas that are susceptible to checkpoint blockade immunotherapy. Among 81 candidate antigens tested, we identify T cells restricted to two known neoantigens simultaneously in tumours, spleens and lymph nodes in tumour-bearing mice.

Cancer Immunology and Immunotherapy: Taking a Place in Mainstream Oncology Keystone Symposia Meeting Summary.

The Keystone Symposia conference on was held at the Fairmont Chateau in Whistler, British Columbia, Canada, on March 19-23, 2017. The conference brought together a sold-out audience of 654 scientists, clinicians, and others from both academia and industry to discuss the latest developments in cancer immunology and immunotherapy. This meeting report summarizes the main themes that emerged during the four-day conference.

Temporally Distinct PD-L1 Expression by Tumor and Host Cells Contributes to Immune Escape.

Antibody blockade of programmed death-1 (PD-1) or its ligand, PD-L1, has led to unprecedented therapeutic responses in certain tumor-bearing individuals, but PD-L1 expression's prognostic value in stratifying cancer patients for such treatment remains unclear. Reports conflict on the significance of correlations between PD-L1 on tumor cells and positive clinical outcomes to PD-1/PD-L1 blockade. We investigated this issue using genomically related, clonal subsets from the same methylcholanthrene-induced sarcoma: a highly immunogenic subset that is spontaneously eliminated in vivo by adaptive immunity and a less immunogenic subset that forms tumors in immunocompetent mice, but is sensitive to PD-1/PD-L1 blockade therapy.

Stable Similariton Generation in an All-Fiber Hybrid Mode-Locked Ring Laser for Frequency Metrology.

Ultrashort pulse lasers constitute an important tool in the emerging field of optical frequency metrology and are enabling unprecedented measurement capabilities and new applications in a wide range of fields, including precision spectroscopy, atomic clocks, ultracold gases, and molecular fingerprinting. We demonstrate the generation of stable 127-fs self-similar pulses at a central wavelength of 1560 nm with 7.14-mW average output power.