Immunotherapy is a promising new therapeutic field that has demonstrated significant benefits in many solid-tumor malignancies, such as metastatic melanoma and non-small cell lung cancer. However, only a subset of these patients responds to treatment. Glioblastoma (GBM) is the most common malignant primary brain tumor with a poor prognosis of 14.6 months and few treatment advancements over the last 10 years. There are many clinical trials testing immune therapies in GBM, but patient responses in these studies have been highly variable and a definitive benefit has yet to be identified. Biomarkers are used to quantify normal physiology and physiological response to therapies. When extensively characterized and vigorously validated, they have the potential to delineate responders from non-responders for patients treated with immunotherapy in malignancies outside of the central nervous system (CNS) as well as GBM. Due to the challenges of current modalities of radiographic diagnosis and disease monitoring, identification of new predictive and prognostic biomarkers to gauge response to immune therapy for patients with GBM will be critical in the precise treatment of this highly heterogenous disease. This review will explore the current and future strategies for the identification of potential biomarkers in the field of immunotherapy for GBM, as well as highlight major challenges of adapting immune therapy for CNS malignancies.

Emerging evidence is demonstrating the extent of T‐cell infiltration within the tumor microenvironment has favorable prognostic and therapeutic implications. Hence, immunotherapeutic strategies that augment the T‐cell signature of tumors hold promising therapeutic potential. Recently, immunotherapy based on intratumoral injection of mannan‐BAM, toll‐like receptor ligands and anti‐CD40 antibody (MBTA) demonstrated promising potential to modulate the immune phenotype of injected tumors. The strategy promotes the phagocytosis of tumor cells to facilitate the recognition of tumor antigens and induce a tumor‐specific adaptive immune response. Using a syngeneic colon carcinoma model, MBTA's potential to augment CD8+ T‐cell tumor infiltrate when administered intratumorally or subcutaneously is demonstrated as part of a whole tumor cell vaccine. Both immunotherapeutic strategies prove effective at controlling tumor growth, prolong survival, and induce immunological memory against the parental cell line. Collectively, the investigation demonstrates MBTA's potential to trigger a potent anti‐tumor immune response.

Preclinical models that reliably recapitulate the immunosuppressive properties of human gliomas are essential to assess immune-based therapies. GL261 murine glioma cells are widely used as a syngeneic animal model of glioma, however, it has become common practice to transfect these cells with luciferase for fluorescent tumor tracking. The aim of this study was to compare the survival of mice injected with fluorescent or non-fluorescent GL261 cells and characterize the differences in their tumor microenvironment. Mice were intracranially implanted with GL261, GL261 Red-FLuc or GL261-Luc2 cells at varying doses. Cytokine profiles were evaluated by proteome microarray and Kaplan-Meier survival analysis was used to determine survival differences. Median survival for mice implanted with 5 × 10 4 GL261 cells was 18 to 21 days. The GL261 Red-FLuc implanted mice cells did not reach median survival at any tumor dose. Mice injected with 3 × 10 5 GL261-Luc2 cells reached median survival at 23 days. However, median survival was significantly prolonged to 37 days in mice implanted with 5 × 10 4 GL261-Luc2 cells. Additionally, proteomic analyses revealed significantly elevated inflammatory cytokines in the supernatants of the GL261 Red-FLuc cells and GL261-Luc2 cells. Our data suggest that GL261 Red-FLuc and GL261-Luc2 murine models elicit an anti-tumor immune response by increasing pro-inflammatory modulators. Glioblastoma (GBM) is the most common malignant primary brain tumor in adults 1. Despite ongoing studies and numerous clinical trials, the prognosis remains poor 2. There is an urgent need to provide these patients with new therapies, as the standard of care treatment has gone unchanged for more than a decade 3. In light of the promising advances made in the area of immune therapy as a treatment for various solid cancers 4-7 , the field of neuro-oncology has embraced immunotherapies for gliomas as a promising area of preclinical and clinical investigation 8. However, recent trials like the Phase III CheckMate-143 9 and Phase III CheckMate-498 10 show poor efficacy despite promising results from pre-clinical studies 11-15. The lack of translation from preclinical to clinical studies illustrates the need for a more rigorous characterization of the pre-clinical models currently being used in the scientific community. The development of novel immune therapeutics is not possible without a reliable preclinical animal model that accurately mimics the complex immune landscape of GBM. Of the various classes of preclinical mouse models, syngeneic models have been indispensable for evaluating immune therapies in GBM 16. Syngeneic murine models are models that rely on allografts of immortalized cancer cells from the same mouse strain from which the model originates.

Glioblastoma is in need of innovative treatment approaches. Immune therapy for cancer refers to the use of the body's immune system to target malignant cells in the body. Such immune therapeutics have recently been very successful in treating a diverse group of cancerous lesions. As a result, many new immune therapies have gained Food and Drug Administration approval for the treatment of cancer, and there has been an explosion in the study of immune therapeutics for cancer treatment over the past few years. However, the immune suppression of glioblastoma and the unique immune microenvironment of the brain make immune therapeutics more challenging to apply to the brain than to other systemic cancers. Here, we discuss the existing barriers to successful immune therapy for glioblastoma and the ongoing development of immune therapeutics. We will discuss the discovery and classification of immune suppressive factors in the glioblastoma microenvironment; the development of vaccine-based therapies; the use of convection-enhanced delivery to introduce tumoricidal viruses into the tumor microenvironment, leading to secondary immune responses; the emerging use of adoptive cell therapy in the treatment of glioblastoma; and future frontiers, such as the use of cerebral microdialysis for immune monitoring and the use of sequencing to develop patient-specific therapeutics. Armed with a better understanding of the challenges inherent in immune therapy for glioblastoma, we may soon see more successes in immune-based clinical trials for this deadly disease.

Effective CD8 + T-cell responses play an important role in determining the course of SIV/HIV viral infection. Here we identified a unique population of dysfunctional CD8 + T-cells in lymphoid tissues and bronchoalveolar lavage (BAL) of rhesus macaques with chronic SIV infection characterized by co-expression of CD6 and PD-1. The frequency of CD6 and PD-1 co-expressing CD8 + T-cells was significantly increased in lymphoid tissues and BAL during chronic SIV infection compared to pre-infection levels. These CD6 + PD-1 + CD8 + T-cells displayed impaired proliferation, cytokine secretion and cytotoxicity compared to their CD6 − PD-1 + CD8 + T cell counterparts. The frequency of CD8 + PD-1 + and CD8 + CD6 − PD-1 + T-cells in the lymph node and bone marrow did not correlate with SIV viral load, whereas the frequency of CD8 + CD6 + PD-1 + T-cells positively correlated with SIV viral load in these tissues highlighting the contribution of CD6 to disease progression. CD6 + PD-1 + CD8 + T-cells expressed elevated levels of SHP2 phosphatase compared to CD6 − PD-1 + CD8 + T-cells providing a potential mechanism by which CD6 may induce T-cell dysfunction during chronic SIV infection. Combined targeting of CD6 and PD-1 effectively revived the CD8 + T-cell proliferative response in vitro suggesting a strategy for potential therapeutic benefit.

Purpose Diffuse midline gliomas are rare midline CNS malignancies that primarily affect children but can also affect adults. While radiation is standard treatment, prognosis remains fatal. Furthermore, due to its sensitive anatomic location, many physicians have been reluctant to perform biopsies without potential for improved prognosis. However, recent advancements in molecular-targeted therapeutics have encouraged greater tissue sampling. While the literature reflects this progress, the landscape of how clinicians actually manage these patients remains unclear. Our goal was to assess the attitudes of current practicing neurosurgical oncologists towards management of adult diffuse midline gliomas, reasons behind their practices, and factors that might influence these practices. Methods We created and distributed a survey with 16 multiple choice and open-ended questions to members of the Tumor Section of the Congress of Neurological Surgeons. Results A total of 81 physicians responded to the survey. Although time since training and volume of glioma patients did not significantly affect the decision to consider clinical trials or to offer biopsy, those that operated on fewer gliomas (< 25/ year) were more likely to cite surgical morbidity as the primary reason not to biopsy these midline locations. Further, surgeons with access to more advanced molecular testing were significantly more likely to consider clinical trial eligibility when offering biopsies. Conclusion Factors that affect the management of diffuse midline gliomas and the role of biopsy are relatively uniform across the field, however, there were a few notable differences that reflect the changes within the neuro-oncology field in response to clinical trials.

B1 cells spontaneously produce protective natural antibodies which provide the first line of defense against a variety of pathogens. Although these natural antibodies share similar autoreactive features with several HIV-1 broadly neutralizing antibodies, the role of B1 cells in HIV/SIV disease progression is unknown. We report the presence of human-like B1 cells in rhesus macaques. During chronic SIV infection, we found that the frequency of splenic CD11b+ B1 cells positively correlated with plasma SIV viral load and exhausted T cells. Mechanistically, we discovered that splenic CD11b+ B1 cells express PD-L2 and IL-10, and were able to induce PD-1 upregulation on CD4+ T cells in vitro. These findings suggest that splenic CD11b+ B1 cells may contribute to the regulation of SIV plasma viral load by enhancing T cell exhaustion. Therefore, understanding the mechanisms that govern their function in rhesus macaques may lead to novel therapeutic strategies for impeding HIV/SIV disease progression.

Abstract:The global challenges resulting from the emergence of numerous resistant pathogenic bacteria have led to a search for alternative therapy ethnomedically. As a result, honey is increasingly valued for its antibacterial activity. In this study, the antibacterial activity of different honey samples was assessed in vitro using agar dilution at different concentration of 5%, 10%, 20%, 30%, 40%, 50%, 75% and 100% (v/v) dilution. The antibacterial activity was also determined by spectrophotometric assay at 620 nm. The result showed that KG honey sample inhibited the different bacterial isolates at a concentration of 5% and LB honey sample inhibited the isolates at 20% while other honey samples inhibited the bacterial isolates at concentrations ranging between 10% and 30% (v/v) dilution of each honey samples. Thus, the minimum inhibitory concentrations ranged between a concentration of 5% and 30% (v/v) dilution even though antibacterial activities concentration ranged from 5% -100% (v/v). Ps. aeruginosa ATCC 15442 was considered the most susceptible of all the test isolates. The increases in the absorbances showed that the bacterial populations in each of the honey samples were reduced as the exposure time increases. The study shows that honey being sold in Nigeria may be used as a therapeutic agent to treat infections as they may be an excellent alternative to curtail the further spreading of multi-drug-resistant microorganisms in Nigeria.