Th9 cells are a subset of CD4 + Th cells that produce the pleiotropic cytokine IL-9. IL-9/Th9 can function as both positive and negative regulators of immune response, but the role of IL-9/Th9 in tumor immunity is unknown. We examined the role of IL-9/Th9 in a model of pulmonary melanoma in mice. Lack of IL-9 enhanced tumor growth, while tumor-specific Th9 cell treatment promoted stronger antitumor responses in both prophylactic and therapeutic models. Th9 cells also elicited strong host antitumor CD8 + CTL responses by promoting Ccl20/Ccr6-dependent recruitment of DCs to the tumor tissues. Subsequent tumor antigen delivery to the draining LN resulted in CD8 + T cell priming. In agreement with this model, Ccr6 deficiency abrogated the Th9 cell-mediated antitumor response. Our data suggest a distinct role for tumor-specific Th9 cells in provoking CD8 + CTL-mediated antitumor immunity and indicate that Th9 cell-based cancer immunotherapy may be a promising therapeutic approach.

Multiple myeloma remains an incurable disease. One of the major problems is that myeloma cells develop drug resistance on interaction with bone marrow stromal cells. In this study, we examined the effects of macrophages (Mvarphis), a type of stromal cells, on myeloma cell survival and response to chemotherapy. We showed that Mvarphi, in particular tumor-associated Mvarphi, is a protector of myeloma cells. The protective effect was dependent on direct contact between Mvarphis and myeloma cells. Mvarphis protected both myeloma cell lines and primary myeloma cells from spontaneous and chemotherapy drug-induced apoptosis by attenuating the activation and cleavage of caspase-dependent apoptotic signaling. These findings are clinically relevant because we found that CD68+ Mvarphis heavily infiltrate the bone marrow of patients with myeloma but not the bone marrow of control patients. Thus, our results indicate that Mvarphis may contribute to myeloma cell survival and resistance to chemotherapeutic treatment in vivo.

BackgroundUnderstanding the composition of the microbial community and its functional capacity during weaning is important for pig production as bacteria play important roles in the pig’s health and growth performance. However, limited information is available regarding the composition and function of the gut microbiome of piglets in early-life. Therefore, we performed 16S rRNA gene and whole metagenome shotgun sequencing of DNA from fecal samples from healthy piglets during weaning to measure microbiome shifts, and to identify the potential contribution of the early-life microbiota in shaping piglet health with a focus on microbial stress responses, carbohydrate and amino acid metabolism.ResultsThe analysis of 16S rRNA genes and whole metagenome shotgun sequencing revealed significant compositional and functional differences between the fecal microbiome in nursing and weaned piglets. The fecal microbiome of the nursing piglets showed higher relative abundance of bacteria in the genus Bacteroides with abundant gene families related to the utilization of lactose and galactose. Prevotella and Lactobacillus were enriched in weaned piglets with an enrichment for the gene families associated with carbohydrate and amino acid metabolism. In addition, an analysis of the functional capacity of the fecal microbiome showed higher abundances of genes associated with heat shock and oxidative stress in the metagenome of weaned piglets compared to nursing piglets.ConclusionsOverall, our data show that microbial shifts and changes in functional capacities of the piglet fecal microbiome resulted in potential reductions in the effects of stress, including dietary changes that occur during weaning. These results provide us with new insights into the piglet gut microbiome that contributes to the growth of the animal.Electronic supplementary materialThe online version of this article (10.1186/s40104-018-0269-6) contains supplementary material, which is available to authorized users.

The bone and immune systems are closely related through cellular and molecular interactions. Because bone-resorbing osteoclasts (OCs) are derived from the monocyte/macrophage lineage, similar to dendritic cells (DCs), we hypothesized that OCs could serve as antigen-presenting cells (APCs) to activate T cells. In this study, OCs were generated from human monocytes with stimulation by receptor activator of nuclear factor kappaB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Results showed that, similar to DCs, OCs express major histocompatibility complex (MHC) classes I and II, and CD80, CD86, and CD40; and uptake soluble antigens. OCs secrete interleukin-10 (IL-10), transforming growth factor-beta (TGF-beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha), but not IL-12p70. OCs present allogeneic antigens and activate both CD4+ and CD8+ alloreactive T cells in an MHC-restricted fashion. OCs also present soluble protein tetanus toxoid to activate autologous CD4+ T cells. These findings indicate that OCs can function as APCs and activate both CD4+ and CD8+ T cells. Thus, our study provides new insight into the effect of OCs on the immune system and may help develop novel strategies for treating diseases such as rheumatoid arthritis and multiple myeloma, which affect both the bone and immune systems.

Recent increases in the demand for mobile devices have stimulated the development of nonvolatile memory devices with high performance. In this Communication, we describe the fabrication of low‐cost, high‐performance, digital nonvolatile memory devices based on semiconducting polymers, poly(o‐anthranilic acid) and poly(o‐anthranilic acid‐co‐aniline). These memory devices have ground‐breaking and novel current–voltage switching characteristics. The devices are switchable in a very low voltage range (which is much less than those of all other devices reported so far) with a very high ON/OFF current ratio (which is on the order of 105). The low critical voltages have the advantage for nonvolatile memory device applications of low operation voltages and hence low power consumption. With this very low power consumption, the devices demonstrate in air ambient to have very stable ON‐ and OFF‐states without any degradation for a very long time (which has been confirmed up to one year so far) and to be repeatedly written, read and erased. Our study proposes that the ON/OFF switching of the devices is mainly governed by a filament mechanism. The high ON/OFF switching ratio and stability of these devices, as well as their repeatable writing, reading and erasing capability with low power consumption, opens up the possibility of the mass production of high performance digital nonvolatile polymer memory devices with low cost. Further, these devices promise to revolutionize microelectronics by providing extremely inexpensive, lightweight, and versatile components that can be printed onto plastics, glasses or metal foils.

Novel digital memory devices were fabricated with a thermally and dimensionally stable polyimide containing carbazole moieties in its side groups by using a simple and conventional solution coating process. The devices exhibit excellent unipolar ON and OFF switching behavior. With very low power consumption, the devices can be repeatedly written, read, and erased in air. The ON/OFF current ratio of the devices is high up to 1011. The high ON/OFF switching ratio and stability of the devices, as well as their repeatable writing, reading, and erasing capability with low power consumption, open up the possibility of the mass production of high performance non‐volatile memory devices at low cost.

The identification of novel tumor-associated antigens, especially those shared among patients, is urgently needed to improve the efficacy of immunotherapy for multiple myeloma (MM). In this study, we examined whether Dickkopf-1 (DKK1), a protein that is not expressed in most normal tissues but is expressed by tumor cells from almost all patients with myeloma, could be a good candidate. We identified and synthesized DKK1 peptides for human leukocyte antigen (

Previous studies demonstrated that circulating dendritic cells (DCs) in myeloma patients were functionally abnormal. However, the phenotype and function of patients' monocyte-derived DCs (MoDCs), which are commonly used for immunotherapy, were poorly defined. This study was undertaken to examine the quality of MoDCs from myeloma patients compared with cells from healthy donors. We found that patient-derived MoDCs are phenotypically and functionally defective. Compared with their normal counterparts, patient-derived, mature MoDCs expressed significantly lower levels of CD1a, CD40, CD80, and HLA-DR and were poor at activating alloreactive T cells, presenting recall antigen, and activating autologous antigen-and myeloma-specific T cells. These abnormalities may be attributed to elevated production of autocrine cytokines such as IL-6, activated p38 and STAT3, and inhibited MEK/ERK signaling pathways in the progenitor cells. Treatment with neutralizing IL-6-specific antibody and, more importantly, p38 inhibitor, or both, could correct these abnormalities. Treating patient-derived cells with these agents not only significantly increased cell yield but also produced MoDCs that were as functional as their normal counterparts. Thus, this study has delineated the mechanistic defects of MoDCs from myeloma patients and identi- IntroductionDendritic cells (DCs) are the sentinels of the immune system. [1][2][3] In their immature state, DCs are distributed primarily in tissues where they efficiently survey for incoming pathogens. Encounter with pathogens leads to DC activation and migration to secondary lymphoid organs, and during the migration they undergo maturation. Mature DCs not only acquire the ability to stimulate quiescent, naive CD4 ϩ and CD8 ϩ T cells and B cells and initiate primary immune responses but can also induce a strong secondary immune response with relatively small numbers of DCs and low levels of antigen. 2 Given their central role in controlling immunity, DCs are logical targets for many clinical situations that involve T cells, such as graft rejection, allergy, autoimmune diseases, resistance to infection and tumors, immunodeficiency, and vaccination.DC-based immunotherapy holds great promise for treating malignancies 4-6 including multiple myeloma (MM). [7][8][9][10] However, preliminary reports of DC-based immunotherapy in human MM have demonstrated minor clinical responses. [7][8][9][10] The lack of effectiveness of DC vaccines in tumor patients may be associated, at least in part, with defects in DCs. [11][12][13][14] Indeed, previous studies showed that the numbers of circulating DCs were significantly lower in patients with MM than in healthy individuals, 14 and the phenotype and function of these cells were also impaired. 13,14 The underlying mechanisms are largely unknown. Using the 5T2 myeloma mouse model, we have recently shown that myeloma cells or tumor-culture conditioning medium (TCCM) were able to inhibit differentiation and function of murine bone marrowderived DCs. 15 However, the phen...