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Two types of immunity, humoral and cellular, offer protection against COVID. Humoral protection, contributed by circulating neutralizing antibodies, can provide immediate protection but decays more quickly than cellular immunity and can lose effectiveness in the face of mutation and drift in the SARS-CoV-2 spike protein. Therefore, population-level seroprevalence surveys used to estimate population-level immunity may underestimate the degree to which a population is protected against COVID. In early 2021, before India began its vaccination campaign, we tested for humoral and cellular immunity to SARS-Cov-2 in representative samples of slum and non-slum populations in Bangalore, India. We found that 29.7% of samples (unweighted) had IgG antibodies to the spike protein and 15.5% had neutralizing antibodies, but at up to 46% showed evidence of cellular immunity. We also find that prevalence of cellular immunity is significantly higher in slums than in non-slums. These findings suggest (1) that a significantly larger proportion of the population in Bangalore, India, had cellular immunity to SARS-CoV-2 than had humoral immunity, as measured by serological surveys, and (2) that low socio-economic status communities display higher frequency of cellular immunity, likely because of greater exposure to infection due to population density.

Genotoxic stress and RAS induce the expression of CD155, a ligand for the immune receptors DNAM-1, CD96 and TIGIT. Here we show that antigen-presenting cells upregulate CD155 expression in response to Toll-like receptor activation. Induction of CD155 by Toll-like receptors depended on MYD88, TRIF and NF-κB. In addition, IRF3, but not IRF7, modulated CD155 upregulation in response to TLR3 signals. Immunization of CD155-deficient mice with OVA and the TLR9 agonist CpG resulted in increased OVA-specific IgG2a/c titers when compared to wild type mice. Splenocytes of immunized CD155-deficient mice secreted lower levels of IL-4 and fewer IL-4 and GATA-3 expressing CD4(+) T cells were present in the spleen of Cd155(-/-) mice. Our data suggest that CD155 regulates T(h)2 differentiation. Targeting of CD155 in immunization protocols using peptides may represent a promising new approach to boost protective humoral immunity in viral vaccines.

In the last decade, numerous studies of immunotherapy for malignant glioma (glioblastoma multiforme) have brought new knowledge and new hope for improving the prognosis of this incurable disease. Some clinical trials have reached Phase III, following positive outcomes in Phase I and II, with respect to safety and immunological end points. Results are encouraging especially when considering the promise of sustained efficacy by inducing antitumor immunological memory. Progress in understanding the mechanisms of tumor-induced immune suppression led to the development of drugs targeting immunosuppressive checkpoints, which are used in active clinical trials for glioblastoma multiforme. Insights related to the heterogeneity of the disease bring new challenges for the management of glioma and underscore a likely cause of therapeutic failure. An emerging therapeutic strategy is represented by a combinatorial, personalized approach, including the standard of care: surgery, radiation, chemotherapy with added active immunotherapy and multiagent targeting of immunosuppressive checkpoints.

Survival of glioma (GBM) patients treated with the current standard of care remains dismal. Immunotherapeutic approaches that harness the cytotoxic and memory potential of the host immune system have shown great benefit in other cancers. GBMs have developed multiple strategies, including the accumulation of myeloid-derived suppressor cells (MDSCs) to induce immunosuppression. It is therefore imperative to develop multipronged approaches when aiming to generate a robust anti-tumor immune response. Herein, we tested whether combining MDSC depletion or checkpoint blockade would augment the efficacy of immune-stimulatory herpes simplex type-I thymidine kinase (TK) plus Fms-like tyrosine kinase ligand (Flt3L)-mediated immune stimulatory gene therapy. Our results show that MDSCs constitute >40% of the tumor-infiltrating immune cells. These cells express IL-4Rα, inducible nitric oxide synthase (iNOS), arginase, programmed death ligand 1 (PDL1), and CD80, molecules that are critically involved in antigen-specific T cell suppression. Depletion of MDSCs strongly enhanced the TK/Flt3L gene therapy-induced tumor-specific CD8 T cell response, which lead to increased median survival and percentage of long-term survivors. Also, combining PDL1 or CTLA-4 immune checkpoint blockade greatly improved the efficacy of TK/Flt3L gene therapy. Our results, therefore, indicate that blocking MDSC-mediated immunosuppression holds great promise for increasing the efficacy of gene therapy-mediated immunotherapies for GBM. [Display omitted] Kamran and colleagues provide compelling evidence that shows that inhibiting the critical immunosuppressive myeloid network in the glioma (GBM) tumor microenvironment enhances the efficacy of the immune stimulatory gene therapy, thereby enabling robust anti-GBM immunity to inhibit brain cancer progression and elicit long-term survival of GBM-bearing mice.

This dissertation examines the public relations roles played by Instagram influencers. Specifically, I explore how social media publics (e.g., followers) perceive influencers. I do so by applying role theory as a primary theoretical lens and apply Cialdini’s principles of persuasion (authority, consistency, scarcity, reciprocity, liking, social proof, and unity) to investigate the experiences and perspectives of social media followers directly. This dissertation addresses the following three research questions by exploring the social media influencer-follower storyline: RQ1: How do social media influencers define ‘social media influencer’?RQ2: How do social media followers engage with social media influencers and what public relations roles do they see them fulfill?RQ3: How do social media influencers–through persuasive principles–exert influence on different publics? These questions contend with, respectively, firstly, how social media followers define a social media influencer, the second is concerned with the nature and frequency of social media followers engagement with social media influencers. The third and final research question answers what sources of influence used by social media influencers are described as persuasive and worthy of support by followers.By answering these questions, the dissertation serves to fulfill the goals of capturing how publics perceive and define social media influencers; what unique roles social media influencers play from a public relations perspective or viewpoint; and finally, the extent and nature of the influence that social media influencers enact in the public space. Given these research questions, I used qualitative methods of inquiry. Specifically, I conducted an initial questionnaire, which was followed up with in-depth interviews and triangulated by a content analysis. The findings, in order of the aforementioned research questions, (1) illuminated how publics define influencers and engage with them on Instagram—as extensions of their social circle akin to family and friends, (2) demonstrated that social media influencers add to the social influence aspect by building a relationships with their publics, and in doing so, (3) showed how Instagram influencers play an important role in participants lives through the platform and engaging with on an almost daily basis. These specific findings are the ones that fulfill the goals of the research project; the rest of the several findings are by-products or offshoots and can serve as future research areas. In the theoretical context, there have been attempts to define exactly what is meant by the term ‘influencer’, especially in a public relations context. This study fulfills the need of showing how social media influencers are perceived by their publics and how they are changing the landscape of public relations functions research and practice. As such, this work explicates the influential roles influencers play in public relations and in doing so contributes to public relations research and practice.In the applied context, this study examines how social media influencers, with their communication, occupation of online spaces, and bonds with their social media users create relationships with publics. The discussion explores the ramifications of the relational power that is exerted by enacting the role of social media influencer in the public relations space. Social media influencers are staking their place, and much of that role has been enacted through the Instagram platform. This study gets directly at the viewpoint of Instagram users, or in other words, the followers of Instagram influencers.

There is a large unmet need for effective therapeutic approaches for glioma, the most malignant brain tumor. Clinical and preclinical studies have enormously expanded our knowledge about the molecular aspects of this deadly disease and its interaction with the host immune system. In this review we highlight the wide array of immunotherapeutic interventions that are currently being tested in glioma patients. Given the molecular heterogeneity, tumor immunoediting and the profound immunosuppression that characterize glioma, it has become clear that combinatorial approaches targeting multiple pathways tailored to the genetic signature of the tumor will be required in order to achieve optimal therapeutic efficacy.

Mutation in isocitrate dehydrogenase (mIDH) is a gain of function mutation resulting in the production of the oncometabolite, R-2-hydroxyglutarate, that inhibits DNA and histone demethylases. The resultant hypermethylation phenotype reprograms the glioma cells transcriptome and elicits profound effects on glioma immunity. We report that in mouse models and human gliomas, mIDH1 in the context of ATRX and TP53 inactivation results in global expansion of the granulocytic myeloid cells compartment. Single-cell RNA-sequencing coupled with mass cytometry analysis revealed that these granulocytes are mainly non-immunosuppressive neutrophils and pre-neutrophils; with a small fraction of polymorphonuclear myeloid-derived suppressor cells. The mechanism of mIDH1 mediated pre-neutrophils expansion involves epigenetic reprogramming which leads to enhanced expression of the granulocyte colony-stimulating factor (G-CSF). Blocking G-CSF restored the inhibitory potential of PMN-MDSCs and enhanced tumor progression. Thus, G-CSF induces remodeling of the inhibitory PMN-MDSCs in mIDH1 glioma rendering them non-immunosuppressive; and having significant therapeutic implication Competing Interest Statement The authors have declared no competing interest.

Glioma patients whose tumors carry a mutation in the Isocitrate Dehydrogenase 1 (IDH1R132H) gene are younger at the time of diagnosis and survive longer. The molecular glioma subtype which we modelled, harbors IDH1R132H, tumor protein 53 (TP53) and alpha thalassemia/mental retardation syndrome X-linked (ATRX) loss. The impact of IDH1R132H on genomic stability, DNA damage response (DDR) and DNA repair in this molecular glioma subtype is unknown. We discovered that IDH1R132H expression in the genetic context of ATRX and TP53 inactivation: (i) increases median survival (MS), (ii) enhances DDR activity via epigenetic upregulation of Ataxia-telangiectasia mutated (ATM) signaling, and (iii) elicits tumor radioresistance. Pharmacological inhibition of ATM or checkpoint kinase 1 and 2 (CHK1/2), two essential kinases in the DDR pathways, restored tumor radiosensitivity. Translation of these findings for mIDH1 glioma patients could significantly improve the therapeutic efficacy of radiotherapy, and thus have a major impact on patient survival.

The 2020 U.S. Census data show a rapidly diversifying U.S. population. We sought to evaluate whether clinical faculty and leadership representation at academic medical schools reflects the diversifying population over time. Using data from the Association of American Medical Colleges for the period of 1977 through 2019, we found notable progress in female representation among clinical faculty, with smaller gains among department chairs and medical school deans. Racial and ethnic groups that are underrepresented in medicine are designated as such because their presence within the medical profession is disproportionate to the U.S. Census data. Even with accounting for this underrepresentation, clinical faculty and leadership positions show even starker disparities. Thoughtful policy implementation could help address this persistent underrepresentation among medical school faculty and leadership positions. An analysis of data from the Association of American Medical Colleges from 1977 through 2019 showed progress in female representation among clinical faculty, full professors, department chairs, and medical school deans. Much less improvement was observed for racial and ethnic groups designated by the AAMC as underrepresented in medicine.