bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract IA15: Role of human papillomaviruses in carcinogenesis
Authors: Tommasino Massimo 
Published: December 2020

Abstract
Infectious agents represent a major group of risk factors for cancer development and contribute to about 15% of human cancers worldwide. Six viruses and one bacterium, i.e., human papillomavirus (HPV), hepatitis C virus (HCV), hepatitis B virus, human T-lymphotropic virus type I (HTLV-1), Epstein-Barr virus (EBV), Kaposi sarcoma-associated virus (KSHV), and Helicobacter pylori, have been clearly associated with human carcinogenesis. The mucosal high-risk (HR) HPV types are the etiologic factors of cervical cancers and subset of oropharyngeal cancers. In addition, ongoing studies concerning a subgroup of HPV types that infect the skin suggest their involvement, together with ultraviolet radiation (or solar exposure), in the development of nonmelanoma skin cancer (NMSC). Biologic studies have demonstrated that the products of two early genes from the HR HPV types, E6 and E7, play a key role in cancer development. Both viral oncoproteins are able to target several cellular pathways leading to the evasion of the immune surveillance and cellular transformation. These studies also substantially contributed to our understanding of key mechanisms involved in the normal life of the cell. In the last few years, we have performed additional studies on cutaneous and mucosal HPV types and have characterized novel oncogenic viral mechanisms involved in the evasion of the immune response and/or in cellular transformation. A few examples will be presented.
Citation Format: Massimo Tommasino. Role of human papillomaviruses in carcinogenesis [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr IA15.
Abstract IA20: Gut microbiota dysbiosis and dietary fermentable fibers in a pickle: A brew for liver cancer
Authors: Vijay-Kumar Matam 
Published: December 2020

Abstract
Dietary soluble fibers are fermented by gut bacteria into short-chain fatty acids (SCFA), which are considered broadly health promoting. Accordingly, consumption of such fibers ameliorates metabolic syndrome in a subset (40%) of Toll-like receptor 5-deficient (TLR5KO) mice. However, incorporating fermentable fiber inulin, but not nonfermentable fiber cellulose, into a compositionally defined purified diet induced hyperbilirubinemia and cholemia as primary clinical symptoms and hallmarks of cholestasis. These cholestatic mice eventually developed robust, multinodular hepatocellular carcinoma (HCC; a type of liver cancer) within 6 months. Inulin-induced HCC progressed via early onset of cholestasis, hepatocyte death, followed by liver inflammation primarily driven by neutrophils. Such neutrophilic inflammation is characterized by elevated levels of neutrophil elastase and myeloperoxidase, and hepatic reactive oxygen species, malondialdehyde and 8-hydroxy-2’-deoxyguanosine, a marker of DNA damage. Pathogenesis of such HCC was microbiota dependent and observed in multiple strains of dysbiotic mice, but not in germ-free or antibiotics-treated TLR5KO mice. Furthermore, inulin-enriched diet induced both dysbiosis and HCC in wild-type (WT) mice co-housed or cross-fostered with TLR5KO mice. Pharmacologic inhibition of fermentation or depletion of fermenting bacteria markedly reduced intestinal SCFA and prevented HCC. Intervening with cholestyramine to prevent enterohepatic recirculation of bile acids also conferred protection against such HCC. Thus, notwithstanding the health benefits of inulin, enrichment of foods with fermentable fiber should be approached with great caution as it may increase risk of HCC and warrants that refined fibers need to be redefined.
Citation Format: Matam Vijay-Kumar. Gut microbiota dysbiosis and dietary fermentable fibers in a pickle: A brew for liver cancer [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr IA20.
Abstract IA22: The role of the intestinal microbiome in allogeneic hematopoietic cell transplantation
Authors: van den Brink Marcel 
Published: December 2020

Abstract
Relationships between microbiota composition and clinical outcomes of patients following allogeneic hematopoietic cell transplantation (allo-HCT) have been described in single-center studies. Geographic variations in the composition of human microbial communities and differences in clinical practices across institutions raise the question of whether these associations are generalizable. Therefore, we studied 8,767 fecal samples from 1,362 allo-HCT patients at four centers on three continents by 16S ribosomal sequencing. In an observational study, we examined associations between microbiota diversity and overall survival during two years of follow-up after allo-HCT with proportional-hazards analysis. We observed reproducible patterns of microbiota disruption characterized by loss of diversity and domination by single taxa. Low diversity in the peri-neutrophil engraftment period was reproducibly associated with increased risk of death (multivariate-adjusted HR 0.48, 95% CI 0.30-0.77, p = 0.002 in the largest cohort). Subset analysis suggested that these reductions in overall survival were in part due to an increased risk of transplant-related mortality and graft-versus-host disease. Baseline pre-HCT samples already bore evidence of microbiome disruption, and low diversity prior to transplantation was associated with poor survival. In addition, we found that Enterococcus faecium dominates the intestinal microbiota of up to 65% allo-HCT patients early after transplant at all four transplant centers. Enterococcus domination was associated with an increased incidence of acute graft-versus-host disease (GVHD), increased GVHD-related mortality, and reduced overall survival. Post-transplant expansion of Enterococci was also observed in mouse models of GVHD in the absence of antibiotic treatment. Spiking a minimal flora with Enterococci in gnotobiotic mice exacerbated lethal GVHD. Metagenomic sequencing of human and murine Enterococcus-dominated fecal samples revealed an enrichment of lactose and galactose degradation genes, a pathway necessary for Enterococcus growth in vitro. A lactose-free chow attenuated the intestinal outgrowth of Enterococcus and reduced the severity of lethal GVHD in mice. In patients, a lactose-nonabsorber genotype was associated with an increased Enterococcus abundance after cessation of antibiotic treatment after allo-HCT. In conclusion, the concordance of microbiota disruption patterns and their associations with clinical outcomes suggest that approaches to manipulate the intestinal microbiota with the aim of improving allo-HCT clinical outcomes may be generalizable.
Citation Format: Marcel van den Brink. The role of the intestinal microbiome in allogeneic hematopoietic cell transplantation [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr IA22.
Abstract IA25: Tumors alter gut microbiota to suppress immunity and foster progression
Authors: Hribe-Herranz Mireia , Bittinger Kyle , Tanes Ceylan , Rafail Stavros , Pierini Stefano , Ben-Joseph Edgar , Tanyi Janos , Facciabene Andrea 
Published: December 2020

Abstract
Immune dysfunction is commonly observed in patients with cancer contributing to tumor progression. While previous work established a connection between the gut microbiota and the immune system, the mechanisms by which microbiotas contribute to cancer-associated immune dysfunction are not well understood. Using multiple mouse cancer models, we demonstrated robust alterations of gut microbiota in tumor-bearing mice and a substantial change in antimicrobial peptides produced by the gut epithelium. We identified an overall reduction in IFN-γ T cells in tumor-bearing mice, which was rescued with antibiotics treatment or by co-housing tumor-bearing mice with healthy mice. Similar to mouse, we observed changes in gut microbiota and antimicrobial peptides levels of patients diagnosed with ovarian or lung cancer. We identify Firmicutes Ruminococcus members as key promoters of immune dysfunctions and tumor development. These findings identify a new mechanism of immune modulation utilized by tumors to undermine the immune responses and promote tumor progression.
Citation Format: Mireia Hribe-Herranz, Kyle Bittinger, Ceylan Tanes, Stavros Rafail, Stefano Pierini, Edgar Ben-Joseph, Janos Tanyi, Andrea Facciabene. Tumors alter gut microbiota to suppress immunity and foster progression [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr IA25.
Abstract IA28: Targeting the microbiome in cancer immunotherapy
Authors: Trinchieri Giorgio 
Published: December 2020

Abstract
Commensal microorganisms colonize barrier surfaces of all multicellular organisms, including those of humans. For more than 500 million years commensal microorganisms and their hosts have coevolved and adapted to each other. As a result, the commensal microbiota affects many immune and nonimmune functions of their hosts, and de facto the two together comprise one metaorganism. The commensal microbiota communicates with the host via biologically active molecules. Recently, it has been reported that microbial imbalance may play a critical role in the development of multiple diseases, such as cancer, autoimmune conditions, and increased susceptibility to infection. The commensal microbiota not only may affect the development, progression, and immune evasion of cancer but has also important effects on the response to cancer immune- and chemotherapy. In my presentation I will discuss some recent analysis of the role of the microbiome in anti-PD1 therapy in melanoma patients, the preliminary data of a fecal microbiota transfer clinical trial (performed at the University of Pittsburgh Cancer Center) in anti-PD1 refractory melanoma patients, as well as mouse data on the effect of dietary fibers on anti-PD1 cancer therapy.
Citation Format: Giorgio Trinchieri. Targeting the microbiome in cancer immunotherapy [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr IA28.
Abstract PR01: Right-sided colonic biofilms are associated with adenoma formation in patients with Lynch syndrome
Authors: Bruggeling Carlijn , Witjes Vera , Garza Daniel , Fransen Milou , Krekels Joyce , Bisseling Tanya , van Kouwen Mariëtte , Hoogerbrugge Nicoline , Lücker Sebastian , Dutilh Bas , Nagtegaal Iris , Boleij Annemarie 
Published: December 2020

Abstract
Colonic bacterial biofilms are an emerging manifestation in colorectal cancer (CRC); they exhibit carcinogenic properties and are frequently present on right-sided cancerous lesions. Whether bacterial biofilms propose a risk factor for early carcinogenesis in humans is yet unresolved. Therefore, we studied bacterial biofilms in tandem with adenoma formation in patients with Lynch syndrome (LS). LS patients carry a pathogenic germline variant in one of the DNA mismatch repair (MMR) genes, resulting in a variable predisposition to develop colonic cancerous lesions. A total of 100 LS patients were included in our study, consisting of 23 MLH1, 24 MSH2, 36 MSH6, and 17 PMS2 MMR variants. During regular screening colonoscopies, normal-appearing forceps biopsies were taken from colon ascendens (right colon) and descendens (left colon). Biopsies were screened for bacterial biofilms using fluorescent in situ hybridization by targeting bacterial 16s rRNA. The frequency of colorectal adenomas (tubular adenomas and [tubulo]villous adenomas) before and during colonoscopy was registered. Overall, 60% of patients presented with a biofilm, of which most were right-sided (right-sided: 25%, both sides: 21%, left-sided: 14%). Interestingly, adenomas were more frequently present in patients with a right-sided biofilm (right-sided: 64%, both sides: 58%) than in patients with a left-sided biofilm (29%) or no biofilm (38%). The occurrence of bacterial biofilms was not correlated with age, BMI, or MMR-variant. Statistical analysis revealed that right-sided bacterial biofilms correlated with right-sided adenomas (Pearson: 0.272, p=0.007) and left-sided adenomas (Pearson: 0.227, p=0.026), while left-sided biofilms were not correlated with left- or right-sided adenomas (Pearson: 0.037, p=0.718 and -.127, p=.213). To model the probability of right-sided adenoma formation, we performed a binary logistic regression analysis and found that age (odds ratio: 1.065 [CI: 1.024; 1.108, p=0.002]) and right-sided biofilms (odds ratio: 3.020 [CI: 1.151; 7.926, p=0.025]) significantly contributed. Our data suggest that right-sided bacterial biofilms are a hallmark for high-risk LS patients and may play a role in early carcinogenesis.
This abstract is also being presented as Poster A06.
Citation Format: Carlijn Bruggeling, Vera Witjes, Daniel Garza, Milou Fransen, Joyce Krekels, Tanya Bisseling, Mariëtte van Kouwen, Nicoline Hoogerbrugge, Sebastian Lücker, Bas Dutilh, Iris Nagtegaal, Annemarie Boleij. Right-sided colonic biofilms are associated with adenoma formation in patients with Lynch syndrome [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr PR01.
Abstract PR10: Candida albicans infection mediates gastrointestinal track malignancy independently of Il17a in an APECED mouse model
Authors: Zhu Feng , Willette-Brown Jami , Phan Trang , Zhao Yongmei , Tran Bao , Filler Scott G. , Lionakis Mihalis S. , Hu Yinling 
Published: December 2020

Abstract
The cytokine Il17a plays an important role in protection against fungal infection, yet it also serves as a pathogenic factor in several inflammation-related cancers. Previously we reported that fungal infection promotes the development of esophageal squamous cell carcinoma (ESCC) in the IKKalpha kinase-dead KA knock-in (KA) mice that mimic a human autoimmune disorder, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Our data showed that KA T cells failed to induce Il17a in response to fungal infection. However, the role of Il17a in fungal infection-mediated esophageal carcinogenesis remains to be further determined. In this study, we crossed KA mice with Il17a-/- mice to generate KA;Il17a-/- double mutant mice. We orally inoculated WT, Il17a-/-, KA, and KA;Il17a-/- mice with Candida albicans weekly for 3 months to investigate gastrointestinal (GI) track tumorigenesis, including the SCC development in the oral cavity, esophagus, and forestomach. We found that loss of Il17a leads to much earlier onset of GI track tumors in KA;Il17a-/- mice than that in KA mice. KA;Il17a-/- mice also died much earlier compared to KA mice, which is likely due to increased C. albicans burden in the absence of Il17a. The incidence of GI track tumors is comparable between KA and KA;Il17a-/- mice, suggesting that C. albicans infection-associated GI track tumorigenesis is independent of Il17a in KA mouse model. To further understand the underlying mechanism, we performed single-cell RNA sequencing analysis for CD45+ immune cells isolated from long-term C. alibicans-infected mouse esophagi of WT, Il17a-/-, KA, and KA;Il17a-/- mouse cohorts. Interestingly, the neutrophil population was significantly increased in the esophagi of KA and KA;Il17a-/- mice compared to WT and Il17a-/- mice. However, KA neutrophils exhibited reduced capacity in killing C. albicans with reduced NETs formation compared to WT neutrophils, suggesting that the defect in NETs formation may play a pivotal role in GI track tumorigenesis in the context of fungal infection. We are currently investigating how the interplay between C. albicans infection and host neutrophils regulates Candida infection-associated GI track tumorigenesis.
This abstract is also being presented as Poster B01.
Citation Format: Feng Zhu, Jami Willette-Brown, Trang Phan, Yongmei Zhao, Bao Tran, Scott G. Filler, Mihalis S. Lionakis, Yinling Hu. Candida albicans infection mediates gastrointestinal track malignancy independently of Il17a in an APECED mouse model [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr PR10.
Abstract IA04: Relating single cell function to tissue structure in human tumors using MIBI-TOF
Authors: Angelo R. Michael 
Published: December 2020

Abstract
Understanding the role of distinct cellular phenotypes in tissue function, development, and pathogenesis requires tools that can rapidly and consistently quantify the expression of multiple proteins while preserving spatial information. To meet this need, we have developed Multiplexed Ion Beam Imaging by Time-Of-Flight (MIBI-TOF). MIBI-TOF uses secondary ion mass spectrometry to visualize up to 50 metal labeled antibodies at subcellular resolution simultaneously with histochemical stains and native biological elements. We have used this capability to study how single cell function and tissue structure interact at the tumor immune microenvironment, the human maternal-fetal interface, and in infectious disease. These studies have led us to develop scalable, automated, and extensible tools for image thresholding, single cell segmentation, cell clustering, and cell neighborhood analyses that can be deployed on any tissue. Through NIH HuBMAP and CIMAC initiatives, we are currently working to deploy this computational pipeline as well as preformulated antibody staining master mixes as a streamlined, end-to-end workflow for routine high dimensional tissue analysis in basic and translational research. Lastly, we are currently working to develop brighter primary ion sources and new metal reporter constructs that will permit full tissue section scanning while extending multiplexed detection to include RNA and DNA.
Citation Format: R. Michael Angelo. Relating single cell function to tissue structure in human tumors using MIBI-TOF [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr IA04.
Abstract IA05: Deciphering the immune microenvironment with spatial histology
Authors: Yuan Yinyin 
Published: December 2020

Abstract
Tumours are complex, evolving ecosystems with dynamic crosstalk among cancer and normal cells. Measuring spatial heterogeneity in the tumour microenvironment is critical for understanding the spatial context in which cancer develops and evolves. I will discuss quantitative spatial histology measures of immune response as a result of combining automated histology image analysis and spatial statistics. Geospatial variation in the immune microenvironment can have profound clinical implications, even in cancers with low immunogenicity, such as estrogen-receptor positive breast cancer. I will also share our recent progress on studying the geospatial complexity of tumour microenvironment in the TRACERx study of lung cancer evolution.
Citation Format: Yinyin Yuan. Deciphering the immune microenvironment with spatial histology [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr IA05.
Abstract IA13: In the light of evolution: Why do we get more cancers in old age?
Authors: Pham-Danis Catherine , Rozhok Andrii , Scarborough Hannah , Little Nathaniel , Henry Curtis , Nemkov Travis , Hansen Kirk , DeGregori James 
Published: December 2020

Abstract
Why do we get cancer? Why is cancer highly associated with old age? Of course, aging is associated with the accumulation of more mutations, and some of these mutations can contribute to cancer phenotypes. But we now understand that carcinogenesis is much more complex than originally appreciated. In particular, there are tissue environmental forces that both impede and promote cancer evolution. Just as organismal evolution is known to be driven by environmental changes, cellular (somatic) evolution in our bodies is similarly driven by changes in tissue environments, whether caused by the normal process of aging, by lifestyle choices or by extrinsic exposures. Environmental change promotes selection for new phenotypes that are adaptive to the new context. In our tissues, aging or insult-driven alterations in tissues drives selection for adaptive mutations, and some of these mutations can confer malignant phenotypes. We have been using mouse models of cancer initiation, mathematical models of cellular evolution, and analyses of human tissue samples to better understand the evolutionary forces that control somatic cell evolution and thus cancer risk. We have shown that aging and inflammation dependent changes in tissue environments dramatically dictate whether cancer-causing mutations are advantageous to stem cells in our tissues, starting the cells down the path to cancer. Our studies have focused on cancer initiation within the hematopoietic system and the lung. These studies have also uncovered molecular explanations for mutation-driven adaptation to aged and inflammatory tissue environments. In all, these studies indicate that strategies to prevent or treat cancers will need to incorporate interventions that alter tissue microenvironments. While we largely cannot prevent mutation accumulation through our lives, we do have the ability to manipulate tissue environments so as to change the evolutionary trajectories of cells with cancer-causing mutations.
Citation Format: Catherine Pham-Danis, Andrii Rozhok, Hannah Scarborough, Nathaniel Little, Curtis Henry, Travis Nemkov, Kirk Hansen, James DeGregori. In the light of evolution: Why do we get more cancers in old age? [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr IA13.
Abstract IA17: Measuring and modeling cancer evolution with single cell approaches
Authors: Shah Sohrab 
Published: December 2020

Abstract
In this talk, I will provide an overview or advances in single cell whole genome sequencing to study the properties of cancer evolution. Using recently published direct library preparation (DLP+) we used scaled timeseries analysis of model systems to derive predictive models of clone-specific fitness. We defined both genetic and pharmacologic perturbations and measured clonal population abundances at single cell resolution over granular time intervals. We then combined the statistical power of phylogenetics and population genetics to quantitate fitness coefficients of distinct clones. We show how our models are predictive through reproducibility experiments and provide a quantitative formalism to interpret the impact perturbations on fitness landscapes. We show that systemic chemotherapy can dramatically alter the fitness properties of cancer cells leading to clone-specific expansion of resistant populations and eradication of high fitness clones in the untreated context. Our results have implication for how to effectively model the impact of drug selection in pre-clinical model systems.
Citation Format: Sohrab Shah. Measuring and modeling cancer evolution with single cell approaches [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr IA17.