bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract IA33: Include Me; I Want to Live!
Authors: Green Bettye L. 
Published: March 2017

Abstract
Include Me; I Want to Live!
We know the barrier to minorities entering clinical trials: knowledge of trials, location of participating researchers, and general understanding of clinical trials. The task before us is how to overcome these barriers to increase enrollment.
Objective:
Find a link to increase enrollment of minorities in clinical trials, while observing and respecting the culture, family values, and religious beliefs of clients.
Working Task:
Interviews with researchers, IRB Boards, staff, advocates and patients. This is not a scientific report, but a personal review of cancer answers and questions; why?, what?, and how?. Collectively, we have to agree it's not working (increased enrollment). We have the tools, and the information to build upon (from programs that work), but yet, we do not have overall increase in enrollment.
Plans for enhancing our knowledge level:
1. Focus groups,
2. Health Fair
3. Community Leader Sessions
4. Dinners, to name a few.
We have to realize the need for thinking outside the box, and acting upon a different course of action. A major concern is continuation, the changes needed are not a one shot deal, but repetition, a new way. We have community workers, but are we using them in the cancer world. Are biggest barrier remains fear.
A set of questions will examine the known barriers and fears with an honest attempt to design new methods to bring about change.
Questions:
1. Do you know about clinical trials?
2. Do you trust the findings of clinical trials?
3. What would allow you to enter in a clinical trial?
4. Why would you place a patient in a trial/why not?
5. What would I have to do for your comfort level involving clinical trials.
This session/report is not to reveal a definite answer, regarding minorities and clinical trials, but looking for a crossover link to enhance a meaningful enrollment method.
Citation Format: Bettye L. Green. Include Me; I Want to Live!. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr IA33.
Abstract IA42: Genome wide association for breast cancer risk in Latinas: Analysis of known susceptibility loci
Authors: Hoffman Joshua , Sawyer Sarah , Fejerman Laura , Hu Donglei , Huntsman Scott , John Esther , Torres-Mejia Gabriela , Kushi Larry , Haiman Chistopher , Ziv Elad 
Published: March 2017

Abstract
Background: Genome wide association studies have identified over 90 common variants associated with breast cancer risk. The majority of these findings have been made in populations of European ancestry. We have performed a genome wide association study of in ~2400 US Latina and Mexican breast cancer cases and ~7500 controls. Here we report on examination of previously reported loci and fine mapping within those loci.
Methods:
Cases and controls included women from the San Francisco Bay Area Study, the Northern California Breast Cancer Family Registry, the Multi-Ethnic Cohort and the Kaiser Permanente Research Program on Genes and the Environment on Health all based in California. In addition we included cases and controls from the CAMA study, based in Mexico and recruiting from 4 different states: Mexico City, Veracruz, Monterrey, and Puebla. Each of the samples were genotyped using an array with genome wide coverage (Affymetrix 6.0, Affymetrix Axiom, Illumina 1M, Illumina 2.5M or Illumina Oncoarray). We inferred genetic ancestry using principal components analysis. We imputed each array to the Haplotype Reference Consortium and performed association testing with breast cancer using logistic regression models, adjusting for study, array used, and principal components 1-10.
Results: We have identified several signals at 6q25 which are independent of previously reported SNPs in other populations. We have also evaluated the utility of polygenic risk using data from common variants at previously reported loci. We compared a range of algorithms to enhance the predictive power of polygenic risk in Latinas, including ones that utilize fine mapping vs. ones which use the top SNPs from other populations.
Conclusion: We demonstrate that a combination of new variants and judicious use of data from the known loci generates useful polygenic risk for breast cancer in Latinas.
Citation Format: Joshua Hoffman, Sarah Sawyer, Laura Fejerman, Donglei Hu, Scott Huntsman, Esther John, Gabriela Torres-Mejia, Larry Kushi, Chistopher Haiman, Elad Ziv. Genome wide association for breast cancer risk in Latinas: Analysis of known susceptibility loci. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr IA42.
Abstract A04: An inflammatory gene signature distinguishes neurofibroma Schwann cells and macrophages from cells in the normal peripheral nervous system
Authors: Choi Kwangmin , Komurov Kakajan , Fletcher Jonathan S. , Jousma Edwin , Cancelas Jose A. , Wu Jianqiang , Ratner Nancy 
Published: March 2017

Abstract
Neurofibromas are benign peripheral nerve tumors driven by NF1 loss in Schwann cells (SCs). Current evidence suggests that an inflammatory environment is critical for neurofibroma development and growth, however the roles of intercellular interactions between SCs and other cells in neurofibroma microenvironment are not clear yet. Neurofibromas contain numerous macrophages. We analyzed gene expression in FACS-sorted SCs and macrophages from wild type nerve and neurofibroma. Nerve macrophage transcriptomes differed from previously defined macrophage sub-populations. In 1-month-old Nf1 mutant nerve, neither SCs nor macrophages significantly differed from their counterparts in normal mice. In 7-month-old neurofibromas, macrophages showed significantly altered gene expression, as did neurofibroma SCs. Computational reconstruction of SC-macrophage molecular networks based on the gene expression data revealed extensive inflammatory-associated signaling and possible interplay between macrophages and Schwann cells. Among these were previously implicated pathways and novel paracrine and autocrine loops involving cytokines, chemokines, and growth factors. Specifically, the data predicted increased cytokine expression and imbalanced type-I/type-II interferon signaling, which were confirmed by protein profiling, and normalized in neurofibroma-bearing mice treated with PEGylated interferon-α2b. These studies identify Nf1 mutant SCs interactions with macrophages, which result in chronic inflammation and neurofibroma, and provide a system in which to study early changes in benign tumorigenesis.
Citation Format: Kwangmin Choi, Kakajan Komurov, Jonathan S. Fletcher, Edwin Jousma, Jose A. Cancelas, Jianqiang Wu, Nancy Ratner. An inflammatory gene signature distinguishes neurofibroma Schwann cells and macrophages from cells in the normal peripheral nervous system. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr A04.
Abstract A23: Development of a novel preclinical model to delineate the role of tumor microenvironment on mechanism of action and efficacy of PD-1 checkpoint blockade
Authors: Chakravarthy Kalyan , Sevilla Raquel , Caniga Michael , Zhang Weisheng , Murtaza Anwar , Moy Lily , Cicmil Milenko 
Published: March 2017

Abstract
Background: The cellular environment in which the tumor exists, also known as tumor microenvironment, includes surrounding blood vessels, immune cells, fibroblasts, signaling molecules, and the extracellular matrix. This microenvironment can contribute to the growth and metastases of tumors, potentially influencing the efficacy of therapeutic agents. Thus, understanding the contribution of the microenvironment on tumorigenesis may enable us to investigate biology and kinetics between tumor and surrounding environment and improve target selection for standalone or combination therapies.
Methods: To interrogate the role of the microenvironment we developed a tumor model in which the tumors can grow inside an air-pouch created in the dorsal part of the mouse. The air-pouch serves as the local microenvironment, which can be modulated by pro or anti-inflammatory stimuli to study the impact of local cells and cytokines on tumor growth as well as the efficacy of therapeutic agents.
Results: Using luciferized mouse colon carcinoma (mc38-LUC2) syngeneic cells, we demonstrate that the kinetics of tumor growth within the air-pouch is similar to standard subcutaneously induced tumor models and was quantified via bioluminescence imaging. Additionally, further characterization of the tumor microenvironment was performed using MR and CT imaging, cytokine expression, and cell phenotyping. Furthermore, we also evaluated checkpoint inhibitor agent targeting the PD-1pathway to evaluate its effect on tumor growth and impact on cellular and cytokine microenvironment.
Conclusions: Taken together, our novel model can facilitate innovative assessment of the mechanism of action of immunomodulatory agents across multiple oncological malignancies and evaluation of next generation therapeutics.
Citation Format: Kalyan Chakravarthy, Raquel Sevilla, Michael Caniga, Weisheng Zhang, Anwar Murtaza, Lily Moy, Milenko Cicmil. Development of a novel preclinical model to delineate the role of tumor microenvironment on mechanism of action and efficacy of PD-1 checkpoint blockade. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr A23.
Abstract A25: High-resolution visualization of immune response across the intact melanoma tumor
Authors: Kumari Sudha , Moynihan Kelly , Irvine Darrell J. 
Published: March 2017

Abstract
Tumor immunotherapy relies on improved anti-tumor activity of the immune cells. Efficacious immunotherapy often correlates with increased CD8+ T cell infiltration within the tumor, subsequently resulting into reduction in tumor growth and morphological remodeling. However, pan- melanoma visualization of immune cell infiltration and associated macro-scale alterations in tumor morphology and vasculature remains extremely challenging. This is largely owing to the dense pigmentation, thick extracellular matrix deposition and friable texture of the tumor, rendering it optically inaccessible using the routine histology and organ clarification techniques. Here, we describe a rapid and inexpensive optical clarification technique that enables examination of immune infiltration as well as vascular changes, both at tissue level as well as single cell-resolution within an intact tumor. The aforementioned technique, termed Tumor-optimized three-dimensional imaging of solvent cleared organs (T-DISCO), combines in vivo fluorescent labeling of the endogenous immune cells with organic solvents-based tissue clarification and eventual image acquisition using a standard confocal microscope. This technique when applied to the B16F10 melanoma model undergoing a multi-component immunotherapy, revealed changes within the tumor microenvironment, including vascular normalization and intra-tumoral trafficking of the T cells. Thus, T-DISCO represents a powerful tool to examine and investigate immune cell behavior deep within the intact tumor.
Citation Format: Sudha Kumari, Kelly Moynihan, Darrell J. Irvine. High-resolution visualization of immune response across the intact melanoma tumor. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr A25.
Abstract A34: Beyond immune checkpoint: First-in-class antibody targeting soluble NKG2D ligand sMIC for cancer immunotherapy
Authors: Wu Jennifer D. , Zhang Jinyu D. , Basher Fahmin , Rubinstein Mark 
Published: March 2017

Abstract
In response to oncogenic insult, human cells were induced to express a family of MHC I-chain related molecules A and B (MICA and MICB, generally termed MIC) on the surface which serve as the ligands for the activating immune receptor NKG2D expressed by all human NK and cytotoxic T cells. Theoretically, engagement of NKG2D by tumor cell surface MIC is deemed to signal and provoke the immune system to eliminate transformed cells. Clinically, almost all advanced tumors in cancer patients produce soluble MIC through proteolytic shedding mediated by metalloproteases, or by release in exosomes derived from the cell membrane. Tumor-derived sMIC is known to be highly immune suppressive and profoundly insults the immune system by downregulating receptor NKG2D expression on effector NK and T cells, driving the expansion of tumor-favoring myeloid suppression cells, skewing macrophages into alternatively activated phenotypes, and perturbing NK cell peripheral maintenance. High levels of serum sMIC significantly correlate with advanced diseases of many types of cancer. These observations clearly endorse sMIC to be a cancer immune therapeutic target. However, due to mice lack homologues to human MIC, this concept was not proven until our recent studies. Using a “humanized” MIC-transgenic spontaneous mouse model which recapitulates the NKG2D-mediated onco-immune dynamics of human cancer patients, we show that neutralizing circulating sMIC with a first-in-field non-blocking antibody B10 that does not block the interaction of MIC with NKG2D revamps endogenous innate and antigen-specific CD8 T cell responses. We show that therapy with the non-blocking sMIC-neutralizing antibody results in effectively debulk of primary tumor and elimination of metastasis, with no observed toxicity. Furthermore, we show that clearing sMIC with the first-in-class neutralizing antibody B10 also enhanced the efficacy of other cancer immunotherapeutic modalities, such as immune checkpoint blockade or adoptive cell-based therapy pre-clinically. Our study has launched a new avenue of cancer immunotherapy which can be readily translated into clinical trials.
Note: This abstract was not presented at the conference.
Citation Format: Jennifer D. Wu, Jinyu D. Zhang, Fahmin Basher, Mark Rubinstein. Beyond immune checkpoint: First-in-class antibody targeting soluble NKG2D ligand sMIC for cancer immunotherapy. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr A34.
Abstract A52: Eradication of large established tumors with combination immunotherapy engaging innate and adaptive immunity
Authors: Moynihan Kelly Dare , Opel Cary , Szeto Gregory , Tzeng Alice , Eric Zhu , Engreitz Jesse , Robert Williams , Rakhra Kavya , Zhang Michael , Rothschilds Adrienne , Kumari Sudha , Kelly Ryan L. , Kwan Byron , Abraham Wuhbet , Hu Kevin , Mehta Naveen , Kauke Monique , Suh Heikyung , Lauffenburger Douglas A. , Wittrup K. Dane , Irvine Darrell J. 
Published: March 2017

Abstract
Checkpoint blockade against CTLA-4 or PD-1 has demonstrated that an endogenous immune response can be stimulated to elicit durable regressions in advanced cancer, but these dramatic responses are currently confined to a minority of patients. This outcome is probably due in part to the complex network of immunosuppressive pathways present in advanced tumors, which are unlikely to be overcome by intervention at a single signaling checkpoint, requiring a counter-directed network of pro-immunity signals. Here we demonstrate a combination immunotherapy that recruits a diverse set of innate and adaptive immune effectors, enabling robust elimination of tumor burdens that to our knowledge have not previously been curable by treatments relying on endogenous immunity. Maximal anti-tumor efficacy required four components: a tumor antigen targeting antibody, an extended half-life IL-2, anti-PD-1, and a powerful T-cell vaccine. This combination elicited durable cures in a majority of animals, formed immunological memory in multiple transplanted tumor models, and induced sustained tumor regression in an autochthonous BRrafV600E/Pten-/- melanoma model. Multiple innate immune cell subsets, CD8+ T-cells, and cross-presenting dendritic cells were critical to successful therapy. Treatment induced high levels of intratumoral inflammatory cytokines and immune cell infiltration, enhanced antibody-mediated tumor antigen uptake, and promoted antigen spreading. These results demonstrate the capacity of an elicited endogenous immune response to destroy large, established tumors and elucidate essential characteristics of combination immunotherapies capable of curing a majority of tumors in experimental settings typically viewed as intractable.
Citation Format: Kelly Dare Moynihan, Cary Opel, Gregory Szeto, Alice Tzeng, Zhu Eric, Jesse Engreitz, Williams Robert, Kavya Rakhra, Michael Zhang, Adrienne Rothschilds, Sudha Kumari, Ryan L. Kelly, Byron Kwan, Wuhbet Abraham, Kevin Hu, Naveen Mehta, Monique Kauke, Heikyung Suh, Douglas A. Lauffenburger, K. Dane Wittrup, Darrell J. Irvine. Eradication of large established tumors with combination immunotherapy engaging innate and adaptive immunity. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr A52.
Abstract A64: Mast cell expressed FcεR beta subunit (MS4A2) is prognostic in lung adenocarcinoma
Authors: Ly Dalam , Zhu Chang-Qi , Cabanero Michael , Tsao Ming-Sound , Zhang Li 
Published: March 2017

Abstract
Background: The context of immune cell infiltrates within the tumor is associated with cancer prognosis. The type of immune cells and their activation state can provide mediators that either promote or inhibit tumor growth. A growing body of evidence suggest the presence of innate immune cells play a role in shaping early tumor growth. In attempts to gain insight into the immune networks that regulate tumorigenesis, we used genome wide expression datasets of patients with resected early stage non-small cell lung cancer (NSCLC) to identify immune-related genes associated with patient survival.
Methods: Gene expression analysis was conducted on microarray datasets from 128 early-stage NSCLC adenocarcinoma resected tumor samples. Limiting analysis to immune-related genes, we identified a minimum gene set that is prognostic for lung adenocarcinoma and validated the gene signature in additional published microarray NSCLC datasets. Using pathway analysis and immunohistochemistry (IHC), we identified a role for mast cell-expressed IgE receptor beta subunit, MS4A2, in lung adenocarcinoma progression.
Results: From an immune-related gene list, we identified a minimal gene signature that was able to separate patients into high or low-risk survival groups. This gene signature was shown to be prognostic for NSCLC adenocarcinoma in nine validation datasets (n=1264, hazard ratio 2.07, 95% confidence interval 1.69-2.53, p&lt;0.0001). Pathway analysis of differentially expressed genes within high or low-risk survival subgroups reveals gene ontologies and immune signatures that are enriched for IgE receptor signaling and mast cells in patients with favourable prognosis. Univariate analysis shows that the IgE receptor complex genes, as well as mast cell specific protease, mast cell carboxypeptidase A, are highly prognostic for survival. We are currently using IHC of matched patient samples to validate receptor localization.
Conclusion: By limiting gene expression analysis to immune-related genes, we identified a minimal gene set that indicate an important role for IgE receptor signaling and mast cells in favourable lung cancer prognosis. Our data highlights the importance of innate immune cells in shaping lung cancer development.
Citation Format: Dalam Ly, Chang-Qi Zhu, Michael Cabanero, Ming-Sound Tsao, Li Zhang. Mast cell expressed FcεR beta subunit (MS4A2) is prognostic in lung adenocarcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr A64.
Abstract A67: Phenotypic and functional dynamics of CD4+CD25+FOXP3+ regulatory T cells in patients with tobacco-related oral squamous cell carcinoma
Authors: Das Satya N. , Aggarwal Sadhna , Sharma Suresh C. 
Published: March 2017

Abstract
Background: Oral squamous cell carcinoma (OSCC) is one of the most common head and neck cancers worldwide. Dysregulation of immune response plays a major role in establishment and development of cancer. CD4+CD25+FoxP3+ regulatory T cells (Tregs) have been reported to downregulate effector immune functions and its inactivation have been associated with development of autoimmune diseases. We therefore investigated the phenotypic and functional dynamics of CD4+CD25+FoxP3+ (Tregs) cells in tobacco-related OSCC patients.
Aim: Aim of the study was to investigate the phenotypic and functional characteristics of Tregs cells in OSCC patients in terms of their subsets, expression of functional markers and cytokine profile etc.
Methods: The phenotypic and functional characteristics of Treg subsets in patients with OSCC were assessed by multicolour flowcytometry. The levels of TGFβ were assessed by realtime PCR and western blot.
Results: An increased (p&lt;0.05) prevalence of Tregs phenotypes (CD4+CD25+, CD4+FoxP3+, CD8+FoxP3+, CD4+CD25+FoxP3+) was observed in the peripheral circulation of OSCC patients that positively correlated with clinicopathological features. The increased frequency of CD4+CD8+CD25+FoxP3+, a unique T cells subset also showed significantly higher prevalence in OSCC patients. Functionally CD4+FoxP3+ Tregs showed skewed expression of IL-2, IL-10 and IL-35 in patients as compared with the normal controls. Higher expression of TGF-β in tumour tissues suggests their dominant role in upregulation of differentiation of Tregs from naive T cells in tumour bearing host. Further enhanced expression of CCR5 and CCR7 on Tregs with upregulation of their ligands (CCL5, CCL19 and CCL21) in tumour cells indicate efficient recruitment and trafficking of Tregs to the tumour site.
Conclusions: Accumulation of heterogeneous subsets of Tregs in the peripheral circulation indicates their suggestive role in immuno-suppression leading to growth and proliferation of OSCC. Therefore manipulation of Tregs can be added to the therapeutic armamentarium for enhancing anti-tumour immunity in OSCC patients.
Note: This abstract was not presented at the conference.
Citation Format: Satya N. Das, Sadhna Aggarwal, Suresh C. Sharma. Phenotypic and functional dynamics of CD4+CD25+FOXP3+ regulatory T cells in patients with tobacco-related oral squamous cell carcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr A67.