As crucial antigen presenting cells, dendritic cells (DCs) play a vital role in tumor immunotherapy. Taking into account the many recent advances in DC biology, we discuss how DCs (1) recognize pathogenic antigens with pattern recognition receptors through specific phagocytosis and through non-specific micropinocytosis, (2) process antigens into small peptides with proper sizes and sequences, and (3) present MHC-peptides to CD4 + and CD8 + T cells to initiate immune responses against invading microbes and aberrant host cells. During anti-tumor immune responses, DC-derived exosomes were discovered to participate in antigen presentation. T cell microvillar dynamics and TCR conformational changes were demonstrated upon DC antigen presentation. Caspase-11-driven hyperactive DCs were recently reported to convert effectors into memory T cells. DCs were also reported to crosstalk with NK cells. Additionally, DCs are the most important sentinel cells for immune surveillance in the tumor microenvironment. Alongside DC biology, we review the latest developments for DCbased tumor immunotherapy in preclinical studies and clinical trials. Personalized DC vaccine-induced T cell immunity, which targets tumor-specific antigens, has been demonstrated to be a promising form of tumor immunotherapy in patients with melanoma. Importantly, allogeneic-IgG-loaded and HLA-restricted neoantigen DC vaccines were discovered to have robust anti-tumor effects in mice. Our comprehensive review of DC biology and its role in tumor immunotherapy aids in the understanding of DCs as the mentors of T cells and as novel tumor immunotherapy cells with immense potential.

This paper presents a novel system to estimate body pose configuration from a single depth map. It combines both pose detection and pose refinement. The input depth map is matched with a set of pre-captured motion exemplars to generate a body configuration estimation, as well as semantic labeling of the input point cloud. The initial estimation is then refined by directly fitting the body configuration with the observation (e.g., the input depth). In addition to the new system architecture, our other contributions include modifying a point cloud smoothing technique to deal with very noisy input depth maps, a point cloud alignment and pose search algorithm that is view-independent and efficient. Experiments on a public dataset show that our approach achieves significantly higher accuracy than previous state-of-art methods.

Epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor involved in homeostatic regulation of normal cells and carcinogenesis of epithelial malignancies. With rapid development of the precision medicine era, a series of new therapies targeting EGFR are underway. Four EGFR monoclonal antibody drugs (cetuximab, panitumumab, nimotuzumab, and necitumumab) are already on the market, and a dozen other EGFR monoclonal antibodies are in clinical trials. Here, we comprehensively review the newly identified biological properties and anti-tumor mechanisms of EGFR monoclonal antibodies. We summarize recently completed and ongoing clinical trials of the classic and new EGFR monoclonal antibodies. More importantly, according to our new standard, we re-classify the complex evolving tumor cell resistance mechanisms, including those involving exosomes, non-coding RNA and the tumor microenvironment, against EGFR monoclonal antibodies. Finally, we analyzed the limitations of EGFR monoclonal antibody therapy, and discussed the current strategies overcoming EGFR related drug resistance. This review will help us better understand the latest battles between EGFR monoclonal antibodies and resistant tumor cells, and the future directions to develop anti-tumor EGFR monoclonal antibodies with durable effects.

Forkhead box class O 3a (FOXO3a) is a transcription factor that has emerged as being a tumor suppressor and longevity factor. The precise regulation of FOXO3a transactivation of target genes is achieved via post-translational modifications (PTMs) and specific protein-protein interactions. The multiple types of PTMs that FOXO3a undergoes, including phosphorylation, acetylation, methylation and ubiquitination, serve important roles in directing its subcellular localization and transcription activity, which are central to the integration of insulin/growth factor signaling and oxidative/nutrient stress signaling. The present review summarizes the modifications of FOXO3a that occur via phosphorylation and acetylation. In addition, the synergistic effect of multiple phosphorylations on FOXO3a and the crosstalk between phosphorylation and acetylation in the regulation of FOXO3a are discussed. These discussions may highlight potential strategies for the prevention of cancer and aging.

Forkhead box O (FOXO) transcription factors play an important role in physiological and pathological processes. Extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) can phosphorylate FOXO and cause its degradation or cytoplasmic retention, respectively, leading to tumorigenesis. In addition, C-Jun N-terminal protein kinase (JNK) can promote FOXO nuclear localization, leading to apoptosis. Using confocal imaging of cells transfected with GFP-FOXO3a, we visualized the dynamic translocation of GFP-FOXO3a from the cytoplasm to the nucleus after UV irradiation in a time- and dose-dependent manner. We also found that UV irradiation caused activation of JNK, which in turn inactivated ERK and Akt, leading to FOXO3a translocation and Bim expression. Our results indicate that nuclear translocation of FOXO3a can be regulated by UV irradiation through the JNK-ERK/Akt pathway.

CD38, as a cell surface antigen is highly expressed in several hematologic malignancies including multiple myeloma (MM) and has been proven to be a good target for immunotherapy of the disease. CD38 is also a signaling enzyme responsible for the metabolism of two novel calcium messenger molecules. To be able to target this multifunctional protein, we generated a series of nanobodies against CD38 with high affinities. Crystal structures of the complexes of CD38 with the nanobodies were solved, identifying three separate epitopes on the carboxyl domain. Chromobodies, engineered by tagging the nanobody with fluorescence proteins, provide fast, simple and versatile tools for quantifying CD38 expression. Results confirmed that CD38 was highly expressed in malignant MM cells compared with normal white blood cells. The immunotoxin constructed by splicing the nanobody with a bacterial toxin, PE38 shows highly selective cytotoxicity against patient-derived MM cells as well as the cell lines, with half maximal effective concentration reaching as low as 10−11 molar. The effectiveness of the immunotoxin can be further increased by stimulating CD38 expression using retinoid acid. These results set the stage for the development of clinical therapeutics as well as diagnostic screening for myeloma.

ObjectiveTo ascertain accurate measurements of, and the relationships between, the normative parameters of the tracheobronchial trees in the Chinese population using multi-slice spiral computed tomography (CT) and multi-planar reconstruction (MPR).Materials and MethodsMeasurements were performed on 2107 patients who underwent thoracic CT scans in the PLA General Hospital. The lengths of the trachea and the main stem bronchi, and the sizes of the subcarinal angle were obtained through CT or MPR imaging. Multi-variance analyses were performed to detect potential correlations between obtained parameters.ResultsThe mean length of the trachea was 104.9 ± 13.4 mm (107.8 ± 13.2 mm for men and 101.4 ± 12.8 mm for women). The mean lengths of the right and left main stem bronchi were 13.6 ± 4.3 and 48.3 ± 6.5 mm, respectively. The right bronchus angle and the left bronchus angle were 34.9 and 42.5 degrees, respectively. Significant gender differences were found in all the parameters measured except for the angle of the right upper lobe bronchus. There are no statistically significant correlations among these parameters.ConclusionsThe normal reference values and the likely ranges of distribution of the tracheobronchial trees in the Chinese population have been established. Significant gender differences exist in the dimensions of the trachea, with the exception of the Right upper bronchial angle (RUA).

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