The Multifaceted Role of Th17 Lymphocytes and Their Associated Cytokines in Cancer

While the role of T helper 17 lymphocytes (Th17) in the pathogenesis of autoimmune diseases and in infectious immunity has been relatively well defined, the impact of these cells and their associated cytokines on cancer development is still under debate. Although multiple reports have indicated that Th17 can promote anticancer immunity, others have argued that these cells may exhibit tumor-promoting properties. This dichotomy in the function of Th17 lymphocytes in cancer may be related to the versatile nature of these cells, being capable of differentiating into either proinflammatory Th1 or suppressive FoxP3-expressing Treg cells or hybrid T cell subsets depending on the underlying environmental conditions. In the current review, we examine the role of Th17 lymphocytes and Th17-associated cytokines in cancer and discuss how factors that control their final lineage commitment decision may influence the balance between their tumor-promoting versus tumor-suppressing properties

Comparing Methods for Creating a National Random Sample of Twitter Users

Twitter data has been widely used by researchers across various social and computer science disciplines. A common aim when working with Twitter data is the construction of a random sample of users from a given country. However, while several methods have been proposed in the literature, their comparative performance is mostly unexplored. In this paper, we implement four common methods to collect a random sample of Twitter users in the US: 1% Stream, Bounding Box, Location Query, and Language Query. Then, we compare the methods according to their tweet- and user-level metrics as well as their accuracy in estimating US population with and without using inclusion probabilities of various demographics. Our results show that the 1% Stream method performs differently than others in tweet- and user-level metrics, and best for the construction of a population representative sample. We discuss the conditions under which the 1% Stream method may not be suitable and suggest the Bounding Box method as the second-best method to use

Functionalized iron oxide nanoparticles for controlling the movement of immune cells

Immunotherapy is currently being investigated for the treatment of many diseases, including cancer. The ability to control the location of immune cells during or following activation would represent a powerful new technique for this field. Targeted magnetic delivery is emerging as a technique for controlling cell movement and localization. Here we show that this technique can be extended to microglia, the primary phagocytic immune cells in the central nervous system. The magnetized microglia were generated by loading the cells with iron oxide nanoparticles functionalized with CpG oligonucleotides, serving as a proof of principle that nanoparticles can be used to both deliver an immunostimulatory cargo to cells and to control the movement of the cells. The nanoparticle-oligonucleotide conjugates are efficiently internalized, non-toxic, and immunostimulatory. We demonstrate that the in vitro migration of the adherent, loaded microglia can be controlled by an external magnetic field and that magnetically-induced migration is non-cytotoxic. In order to capture video of this magnetically-induced migration of loaded cells, a novel 3D-printed “cell box” was designed to facilitate our imaging application. Analysis of cell movement velocities clearly demonstrate increased cell velocities toward the magnet. These studies represent the initial step towards our final goal of using nanoparticles to both activate immune cells and to control their trafficking within the diseased brain

Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016

Doxorubicin and T Helper Lymphocytes: Unexpected Allies Against Cancer

Despite considerable progress in conventional cancer therapies, major challenges persist in the treatment of patients with advanced stage malignancies. Cancer immunotherapy (harnessing the immune system against tumors) has demonstrated limited success to date, partially due to the immunosuppressive environment generated by tumors. The mechanisms of cancer-induced immune suppression are multiple and include the promotion of immunosuppressive cells such as regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC). MDSC expand in tumor-bearing hosts and play a central role in cancer immune evasion by inhibiting adaptive and innate immunity. Different approaches have been explored to negatively impact MDSC, each associated with specific pitfalls. In this study, we demonstrated that the anthracycline doxorubicin selectively eliminates MDSC in the spleen, blood and tumor beds. Furthermore, five days after doxorubicin treatment residual MDSC exhibited impaired suppressive function, which correlated with reduced reactive oxygen species (ROS) production, and down-regulation of arginase-1 and indoleamine 2,3-dioxygenase (IDO) expression. Of therapeutic relevance, the frequency of effector lymphocytes (CD4⁺ and CD8⁺ T cells) or natural killer cells (NK) to suppressive MDSC ratios was significantly increased following doxorubicin treatment of tumor-bearing mice. Importantly, the proportion of natural killer (NK) and cytotoxic T cells (CTL) expressing perforin and granzyme B and of CTL producing IFNγ was augmented following doxorubicin administration. The mechanism of doxorubicin-mediated elimination of MDSC was partly mediated by the increase of ROS production in MDSC at earlier time points after doxorubicin treatment. Consistently, MDSC isolated from gp91-/- mice were less sensitive to doxorubicin in vitro, and doxorubicin effects on MDSC in gp91-/- tumor-bearing mice were reduced. Of clinical significance, this drug efficiently combined with Th1 or Th17 lymphocytes to suppress tumor development and metastatic disease, resulting in better overall survival. MDSC isolated from patients with different types of cancer were also sensitive to doxorubicin-mediated cytotoxicity in vitro. Our results therefore indicate that doxorubicin may be used not only as a direct cytotoxic drug against tumor cells, but also as a potent immunomodulatory agent that selectively impairs MDSC-induced immunosuppression, thereby fostering the efficacy of T cell-based immunotherapy

Editorial: Tumor-promoting immune cells: Cancer immune escape and beyond

International audienceNo abstract availabl

Selective uptake of multi-walled carbon nanotubes by tumor macrophages in a murine glioma model

Carbon nantotubes (CNTs) are emerging as a new family of nanovectors for drug and gene delivery into biological systems. To evaluate potential application of this technology for brain tumor therapy, we, studied uptake and toxicity of multi-walled CNTs (MWCNTs) in the GL261 murine intracranial glioma model. Within 24 h of a single intratumoral injection of labeled MWCNTs (5 µg), nearly 10-20% of total cells demonstrated CNT internalization. Most CNT uptake, however, occurred by tumor-associated macrophages (MP), which accounted for most (75%) MWCNT-positive cells. Within 24 h of injection, nearly 30% of tumor MP became MWCNT-positive. Despite a transient increase in inflammatory cell infiltration into both normal and tumor-bearing brains following MWCNT injection, no significant toxicity was noted in mice, and minor changes in tumor cytokine expression were observed. This study suggests that MWCNTs could potentially be used as a novel and non-toxic vehicle for targeting MP in brain tumors