bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B88: Combination therapy of reovirus and checkpoint inhibition
Authors: Zaidi Shane , Shim Kevin , Rajani Karishma , Diaz Rosa , Ilett Elizabeth , Kottke Timothy , Thompson Jill , Selby Peter , Harrington Kevin , Pandha Hardev , Melcher Alan , Coffey Matt , Vile Richard 
Published: October 2015

Abstract
We have developed the use of reovirus as a systemically delivered oncolytic agent in both pre-clinical models and in Phase I and II clinical trials. Reovirus has direct oncolytic activity against many human/murine tumor cells, partly because of disruption of the PKR-mediated anti-viral response in malignant cells. In addition however, we have shown that anti-tumor therapy is directly associated with immune activation by virus replication in tumors. The immune mechanisms of therapy include both innate immune activation against virally infected tumor cells, as well as the generation of adaptive anti tumor immune responses as a result of in vivo priming against tumor associated antigens released during that killing. Therefore, to exploit the immune components of reovirus anti-tumor therapy, we tested the combination of oncolytic therapy with systemic checkpoint inhibition. To do this, we used our murine, immune-competent, model and a protocol in which injection of reovirus into subcutaneous (s.c.) B16 melanomas generates moderate therapy following intra-tumoral injection of reovirus into 5d established subcutaneous B16 melanomas growing in C57Bl/6 mice. In this model, provision of systemic anti-PD-1 antibody along with i.t. reovirus, significantly enhanced survival compared to i.t. reovirus alone (p&lt;0.01) and led to &gt;40% of mice being cured long term. Immune analysis suggests that the enhanced therapeutic benefit of reovirus plus checkpoint inhibition is contributed by at least two factors. Thus, blockade of PD-1 significantly enhanced the ability of NK cells to recognize (TNF-α secretion), and kill, reovirus-infected target tumor cells. Second, antiPD-1 antibody led to a significant reduction in Treg activity in reovirus-treated mice, with the overall effect of increasing the adaptive CD8+ anti tumor T cell response. We also showed that timing of the checkpoint inhibitor antibody was significant in balancing toxicity with anti tumor therapy. These data suggest that combination of checkpoint inhibition therapy with reovirus oncolytic/immunotherapy represents a readily translatable method to enhance the therapeutic value of either alone.
Citation Format: Shane Zaidi, Kevin Shim, Karishma Rajani, Rosa Diaz, Elizabeth Ilett, Timothy Kottke, Jill Thompson, Peter Selby, Kevin Harrington, Hardev Pandha, Alan Melcher, Matt Coffey, Richard Vile. Combination therapy of reovirus and checkpoint inhibition. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr B88.
Abstract IA02: The intersection of inflammation, immunity, and cancer: From basic biology to translational research
Authors: Karin Michael 
Published: October 2015

Abstract
In addition to endogenous genetic alterations, malignant progression and therapeutic responses are strongly modulated by the innate and adaptive immune systems. Androgen depletion and malignant progression induce lymphocyte recruitment into prostate cancer (PC). Recruited B cells produce lymphotoxin (LT), an inflammatory cytokine that stimulates expansion of androgen-deprived PC progenitors. Recruited B cells also control the response of PC to the immunogenic chemotherapeutic agent oxaliplatin, which at a low, non-myelosuppressive dose, induces immunogenic cell death that promotes generation of tumor-directed cytotoxic T cells (CTL). In three different mouse PC models the resulting tumors do not respond to low dose oxaliplatin unless grown in B cell-deficient hosts. The B lymphocytes responsible for immunosuppression are plasma cells that express IgA, IL-10 and PD-L1, but not LT, whose appearance depends on TGFβ-receptor (TGFβR) signaling. Elimination of these cells, which also infiltrate human therapy-resistant PC, facilitates CTL-dependent eradication of oxaliplatin-treated tumors.
References:
Ammirante, M., Kuraishy, A.I., Shalapour, S., Strasner, A., Ramirez-Sanchez, C., Zhang, W., Shabaik, A., and Karin, M. (2013). An IKKalpha-E2F1-BMI1 cascade activated by infiltrating B cells controls prostate regeneration and tumor recurrence. Genes Dev 27:1435-1440.
Ammirante, M., Luo, J.L., Grivennikov, S., Nedospasov, S., and Karin, M. (2010). B-cell-derived lymphotoxin promotes castration-resistant prostate cancer. Nature 464:302-305.
Grivennikov, S.I., Greten, F.R., and Karin, M. (2010). Immunity, inflammation, and cancer. Cell 140:883-899.
Citation Format: Michael Karin. The intersection of inflammation, immunity, and cancer: From basic biology to translational research. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr IA02.
Abstract IA11: T cell exclusion in pancreatic ductal adenocarcinoma: The FAP+ cancer-associated fibroblast and CXCL12
Authors: Fearon Douglas T. , Pommier Arnaud , Ludwig Michael , Tuveson David 
Published: October 2015

Abstract
Patients with pancreatic adenocarcinoma (PDA), unlike those with melanoma, non-small cell lung cancer and renal cell carcinoma, did not have objective responses to the T cell checkpoint antagonists, antibodies to CTLA-4 and PD-L1, that promote the anti-cancer function of T cells. We sought the basis for this phenomenon by examining the interaction between the immune system and PDA in a genetically engineered mouse model of this disease, the KrasLSL.G12D/+; p53R172H/+; PdxCreTg/+ (or KPC) model. PDA in KPC mice, as in human patients, is resistant to therapy with anti-CTLA-4 and anti-PD-L1, respectively. The explanation for this resistance of the PDA to immune therapy was shown not to be the absence of an anti-cancer cell adaptive immune response, but to be the exclusion of T cells from the vicinity of cancer cells within tumors. The exclusion was caused by the chemokine, CXCL12, that was produced by the carcinoma-associated fibroblasts that were identified by their expression of the membrane protein, FAP. Remarkably, CXCL12 was physically associated with the cancer cells, which were not producing the chemokine. Inhibiting the interaction of this CXCL12 with its receptor, CXCR4, on T cells by administering the drug, AMD3100, caused the rapid accumulation of T cells amongst cancer cells, uncovered the efficacy of anti-PD-L1, and greatly diminished the numbers of cancer cells within the PDA tumors after 6 days of treatment. Thus, pharmacological targeting of the CXCR4-CXCL12 interaction overcomes the dominant immune suppressive mechanism of T cell exclusion in murine PDA. This finding may be relevant to therapy of human PDA, which also exhibits T cell exclusion, coating of cancer cells with CXCL12, and, as noted above, resistance to anti-PD-L1.
Citation Format: Douglas T. Fearon, Arnaud Pommier, Michael Ludwig, David Tuveson. T cell exclusion in pancreatic ductal adenocarcinoma: The FAP+ cancer-associated fibroblast and CXCL12. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr IA11.
Abstract IA13: Microbiota associations in colon cancer
Authors: Sears Cynthia L. 
Published: October 2015

Abstract
Sporadic colorectal cancer (CRC) results from accumulated DNA mutations in colonic epithelial cells but the factors inducing the causative DNA mutations are unclear. One prime local consideration is the microbiota but little is known about how the microbiota may influence colon carcinogenesis. To further understand the relationship between the microbiota and the colonic epithelium in CRC hosts and non-cancer hosts, we studied the microbiota organization in Carnoy's fixed tissues that preserve the mucus layer of the colonic epithelium and the community composition through microbiome profiling. Unexpectedly, we identified a broad regional change in microbiota organization on colon tissues of the CRC host with invasive polymicrobial bacterial biofilms found commonly on both surgically-resected tumors and normal tissue from the proximal colon. Bacterial biofilms were associated with changes in tissue biology predicted to contribute to colon carcinogenesis. In contrast, the non-tumor host colon epithelial samples did not reveal geographic localization of biofilm formation. High throughput sequencing did not reveal consistent bacterial community membership associated with tumors, regardless of biofilm status. Colon mucosal biofilm detection may contribute to risk for development of sporadic CRC.
Citation Format: Cynthia L. Sears. Microbiota associations in colon cancer. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr IA13.
Abstract IA22: Regulation of metabolic plasticity in effector T cells
Authors: Jones Russell Graham 
Published: October 2015

Abstract
T lymphocytes are central effectors of the adaptive immune response, and their proper function is critical for long-lasting immunity to foreign pathogens and tumor immunosurveillance. One of the fundamental programs triggered by T cell activation is the reprogramming of cellular metabolism, which is essential to support the bioenergetic and biosynthetic demands of effector T (Teff) cell function. While often considered a “housekeeping” function, cellular metabolism has recently been linked to proper Teff cell differentiation and effector function in vivo, raising the idea that nutrient availability can be immunomodulatory. However, how nutrient availability shapes T cell metabolism and function remains poorly understood. Here we present evidence suggesting that effector T cells possess “metabolic plasticity” and are capable of altering their metabolic programs in response to nutrient availability. We show that T cells possess a glucose-sensitive metabolic checkpoint controlled by the energy sensor AMP-activated protein kinase (AMPK) that regulates cellular bioenergetics and T cell viability. Effector T cells lacking AMPKα1 display reduced mitochondrial bioenergetics and cellular ATP in response to glucose limitation in vitro or pathogenic challenge in vivo. Finally, we find that AMPKα1 is essential for robust CD4+ and CD8+ T cell responses to viral and bacterial infections in vivo. Our data highlight AMPK-dependent regulation of metabolic homeostasis as a key regulator of T cell-mediated adaptive immunity. These results and the use AMPK agonists to regulate T cell function will be discussed.
Citation Format: Russell Graham Jones. Regulation of metabolic plasticity in effector T cells. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr IA22.
Abstract IA24: Vaccines targeting innate immune cells
Authors: Bhardwaj Nina 
Published: October 2015

Abstract
Targeting dendritic cells (DCs) for immunotherapy represents a powerful approach for harnessing the patient's own immune system to eliminate cancer cells or to limit chronic infection. Immunostimulatory DCs as vaccine adjuvants have been applied and tested in both conditions, with some encouraging results. However, immune suppression mediated by tumors and the tumor microenvironment or chronic viral infection, limits the potential of DC based vaccines and compromises DC activity and that of other innate immune cells in the TME. Targeting DC in situ represents another approach to boost immunity in vivo. Along these lines, DC targeted approaches include antibodies that bind DC receptors and agonists or alarmins that prime DC via multiple pattern recognition receptors. The presentation will address the activities of some of these various agents and the imprinting of adjuvant activity upon DC in vitro and in clinical trials. Combining DC targeted vaccines with new approaches that enhance immunogenicity and overcome the regulatory mechanisms underlying peripheral tolerance may be the key to achieving effective and durable immune responses that translate to better clinical outcomes.
Citation Format: Nina Bhardwaj. Vaccines targeting innate immune cells. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr IA24.
Abstract IA25: Mechanisms of protective tumor immunity
Authors: Dranoff Glenn 
Published: October 2015

Abstract
Efficacious cancer immunotherapies will likely require combinations of strategies that enhance tumor antigen presentation and antagonize negative immune regulatory circuits. We demonstrated that vaccination with irradiated, autologous melanoma cells engineered to secrete GM-CSF followed by antibody blockade of CTLA-4 accomplishes clinically significant tumor destruction with minimal toxicity in a majority of stage IV metastatic melanoma and some advanced ovarian carcinoma patients. The extent of tumor necrosis in post-treatment biopsies was linearly related to the natural logarithm of the ratio of infiltrating CD8+ effector T cells to FoxP3+ Tregs, suggesting that further Treg inhibition might increase the frequency of clinical responses. Through an analysis of cytokine deficient mice, we delineated a critical role for GM-CSF in Treg homeostasis. GM-CSF is required for the expression of the phosphatidylserine binding protein MFG-E8 in antigen presenting cells, whereas the uptake of apoptotic cells by phagocyte-derived MFG-E8 maintains peripheral Treg activity. The pharmacologic inhibition of MFG-E8 function through genetic or engineering-based approaches blocks Treg induction, which intensifies vaccine-induced responses, leading to the regression of established tumors in mice. The clinical translation of these therapeutic strategies to Phase I testing in humans is underway.
The detailed analysis of patients achieving sustained clinical benefits from irradiated, autologous GM-CSF secreting tumor cell vaccines and CTLA-4 antibody blockade also affords a rich opportunity to identify antigens associated with immune-mediated tumor destruction and to delineate mechanisms of therapeutic immunity. In this regard, we have identified antibodies against a panel of secreted and cell surface proteins that play important roles in tumor development and immune evasion. Isolation of the rare, antigen-specific memory B cells directed towards these important targets provides new opportunities for developing human monoclonal antibodies for cancer immunotherapy.
Citation Format: Glenn Dranoff. Mechanisms of protective tumor immunity. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr IA25.
Um jardim florido? A vegetação cultivada em quintais urbanos através de um gradiente social
Authors: Angeoletto Fabio , Santos Jeater Waldemar Maciel Correa , Ruiz Sanz Juan Pedro 
Published: October 2015

Quintais residenciais urbanos possuem um potencial considerável para a conservação da biodiversidade e para a melhoria da qualidade de vida humana. Não obstante, esses espaços não são planificados, e existe pouca informação sobre a diversidade da flora presente nos quintais de moradores de diferentes classes sociais. Quantificamos e comparamos a diversidade vegetal dos quintais de dois bairros da Região Metropolitana de Maringá (RMM), a saber, Jardim das Torres e Zona 02, mediante a identificação das espécies e através do cálculo de índices de diversidade e de correlações bivariadas. Os padrões de diversidade são assaz distintos, quando comparados os bairros, pelo que traçamos diretrizes de planejamento com o objetivo de aumentar a presença de vegetação na RMM, contribuir à conservação da biodiversidade, e, assim, de seus benefícios aos cidadãos.
Endovascular Treatment for Acute Ischemic Stroke in the Setting of Anticoagulation
Authors: Rebello Letícia C. , Haussen Diogo C. , Belagaje Samir , Anderson Aaron , Frankel Michael , Nogueira Raul G. 
Published: October 2015

Background and Purpose—
Oral anticoagulation (OAC) plays a major role in atrial fibrillation stroke prevention but represents a contraindication to intravenous tissue-type plasminogen activator. Intra-arterial therapy remains a potential reperfusion strategy in these patients; however, supporting data are scarce.

Methods—
Retrospective analysis of prospectively collected consecutive intra-arterial therapies from October 2010 to March 2015 comparing OAC (vitamin-K antagonists and novel oral anticoagulants) versus normal hemostasis versus intravenous tissue-type plasminogen activator patients. Primary safety end point is parenchymal hematoma. Secondary safety end point is 90-day mortality. Efficacy end points are successful reperfusion (modified Thrombolysis in Cerebral Infarction, 2b-3) and good outcome (90-day modified Rankin Scale score of 0–2). Logistic regression for predictors of parenchymal hematoma was performed.

Results—

A total of 604 patients were qualified for the study. Baseline and outcomes variables were overall similar for vitamin-K antagonists (n=29) and novel oral anticoagulants (n=17) patients. When compared with normal hemostasis (n=265) and intravenous tissue-type plasminogen activator (n=297), OAC (n=46) patients were older and had more comorbidities. There were no statistically significant differences in the rates of parenchymal hematoma (8% versus 5%;
P
=0.42), 90-day modified Rankin Scale score of 0 to 2 (30% versus 40%;
P
=0.26), and 90-day mortality (32% versus 26%;
P
=0.46) among OAC and normal hemostasis patients. Similarly, there were no significant differences between OAC and intravenous tissue-type plasminogen activator patients in terms of parenchymal hematoma (8% versus 4%;
P
=0.16), 90-day modified Rankin Scale score of 0 to 2 (30% versus 43%;
P
=0.13), and 90-day mortality (32% versus 22%;
P
=0.18). The use of OAC was not associated with the occurrence of parenchymal hematoma on multivariate logistic regression analysis.

Conclusions—
Intra-arterial therapy seems to be safe in patients taking OACs; however, our study showed a nonsignificant increase in hemorrhage and mortality with a nonsignificant decrease in good outcomes in comparison with non-OAC patients. Although these nominal differences may have been related to older age and more comorbidities in the OAC group, larger studies are needed to confirm our findings given our limited sample size.
HYDRA2: A Multispectral Data Analysis Toolkit for Sensors on Suomi-NPP and Other Current Satellite Platforms
Authors: Rink Tom , Menzel W. Paul , Gumley Liam , Strabala Kathy 
Published: October 2015

Abstract
The Hyperspectral Data Viewer for Development of Research Applications, version 2 (HYDRA2), is a freeware-based multispectral analysis toolkit for satellite data that assists scientists in research and development, as well as education and training of remote sensing applications. HYDRA2 users can explore and visualize relationships between sensor measurements (brightness temperatures for infrared and reflectances for visible/near-infrared wavelengths) using spectral diagrams, cross sections, scatterplots, multiband combinations, and color enhancements on a pixel-by-pixel basis.
HYDRA2 can be used with direct broadcast and archived data from sensors on board the National Oceanic and Atmospheric Administration (NOAA)/National Aeronautics and Space Administration (NASA) Suomi–National Polar-Orbiting Partnership (Suomi-NPP), NASA Aqua/Terra, European Organisation for the Exploitation of Meteorological Satellites (EUMETSAT) Meteorological Operational (MetOp), and Chinese Fengyun-3 platforms.
This paper describes HYDRA2 and presents some examples using data retrievals from the Suomi-NPP Visible Infrared Imaging Radiometer Suite (VIIRS), Cross-Track Infrared Sounder (CrIS), Advanced Technology Microwave Sounder (ATMS), and Terra/Aqua Moderate Resolution Imaging Spectroradiometer (MODIS) instruments.
Climate Drivers Linked to Changing Seasonality of Alaska Coastal Tundra Vegetation Productivity
Authors: Bieniek Peter A. , Bhatt Uma S. , Walker Donald A. , Raynolds Martha K. , Comiso Josefino C. , Epstein Howard E. , Pinzon Jorge E. , Tucker Compton J. , Thoman Richard L. , Tran Huy , Mölders Nicole , Steele Michael , Zhang Jinlun , Ermold Wendy 
Published: October 2015

Abstract
The mechanisms driving trends and variability of the normalized difference vegetation index (NDVI) for tundra in Alaska along the Beaufort, east Chukchi, and east Bering Seas for 1982–2013 are evaluated in the context of remote sensing, reanalysis, and meteorological station data as well as regional modeling. Over the entire season the tundra vegetation continues to green; however, biweekly NDVI has declined during the early part of the growing season in all of the Alaskan tundra domains. These springtime declines coincide with increased snow depth in spring documented in northern Alaska. The tundra region generally has warmed over the summer but intraseasonal analysis shows a decline in midsummer land surface temperatures. The midsummer cooling is consistent with recent large-scale circulation changes characterized by lower sea level pressures, which favor increased cloud cover. In northern Alaska, the sea-breeze circulation is strengthened with an increase in atmospheric moisture/cloudiness inland when the land surface is warmed in a regional model, suggesting the potential for increased vegetation to feedback onto the atmospheric circulation that could reduce midsummer temperatures. This study shows that both large- and local-scale climate drivers likely play a role in the observed seasonality of NDVI trends.