bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of IL-17 during Helicobacter pylori infection (MPF2P.750)
Authors: Contreras Diana , Patel Rachna , Algood Holly 
Published: January 2023

Abstract
Helicobacter pylori is a bacterium found in the gastric microbiota of a large percentage of the world’s population. H. pylori colonization results in mild inflammation in all patients, however some patients go on to develop peptic ulcers and gastric cancer. An effective adaptive immune response, which involves a mixed T helper (Th)1, Th17 and Treg response, is essential to minimize colonization but is also responsible for the increased inflammation. Th17 cells, which produce IL-17A, IL-17F, IL-21 and IL-22, are believed to be one of the driving immune cells in response to H. pylori infection. The purpose of our study was to investigate the differential roles of IL-17A, IL-17F, and IL-17A/F in controlling H. pylori colonization and H. pylori-induced gastritis. To this end, IL-17A, IL-17F, and IL-17A/F deficient mice were infected with H. pylori strain PMSS1. After 3 months of infection, the ability of wild-type mice and cytokine deficient mice to control colonization and activate T and B cell responses was assessed. Analyses included measurement of pro-inflammatory cytokines, antibody production, inflammation, and colonization. The pathology suggests that any deficiency of IL-17 leads to increased inflammation and increased cytokine production by other types T helper cells. Although inflammation is beneficial in keeping a low bacterial burden, increased inflammation during IL-17 deficiency may be a key factor in the adverse outcomes of some patients.
Local antigen and inflammation in the lung induce the preferential establishment and maintenance of CXCR6 and CD49a-expressing antigen-specific CD8 TRM cells in the lung parenchyma and airways (MUC1P.900)
Authors: McMaster Sean , Wilson Jarad , Wein Alex , Dunbar Paul , Matloubian Mehrdad , Kohlmeier Jacob 
Published: January 2023

Abstract
Acting as sentinels capable of quickly organizing a secondary immune response upon pathogen challenge, resident memory CD8 T (TRM) populations are initially primed by microenvironment cues and APC licensing following acute infection of peripheral tissues. Despite their capacity for heterologous protection against influenza virus (flu) challenge, scant knowledge exists as to factors necessary to establish and maintain airway and lung parenchymal (LP) CD8 TRM cells. In contrast to mechanisms described for other tissues, lung CD8 TRM cell establishment required cognate antigen recognition once cells were recruited to the lung by local inflammation. Furthermore, this combination of local antigen and inflammation formed long-lasting TRM populations in the LP and airways that highly express the chemokine receptor CXCR6 and adhesion molecule CD49a. During a primary intranasal (IN) flu infection, CXCR6 is preferentially expressed on virus-specific CD8 T cells in the airways and LP by day 7 post-infection. Selectively, LP CD8 TRM cells highly express CXCR6, while systemically circulating flu-specific cells achieve only an intermediate expression level. Finally, use of mixed bone marrow chimeras show that wild-type virus-specific memory CD8 T cells predominate over CXCR6-/- cells in the airway and LP after IN infection with Sendai or flu virus. Thus, our data show that local antigen and inflammation coupled with CXCR6 expression is key to establish CD8 TRM cells in the LP and airways.
Respiratory exposures to pneumococcus establish localized memory capable of heterotypic lung protection (MUC1P.914)
Authors: Stauffer Nicole , Coleman Fadie , Hilliard Kristie , Yamamoto Kazuko , Zabinski Mary , Jones Matthew , Quinton Lee , Mizgerd Joseph 
Published: January 2023

Abstract
Pneumonia is a persistent and pervasive public health burden, often caused by diverse serotypes of Streptococcus pneumoniae. We hypothesize that repeated respiratory infections establish capsule-independent adaptive immunity that protects against subsequent unrelated pneumococcal pneumonia. We have established a mouse model in which mice are infected with diverse pneumococci in the respiratory tract, given time to recover, and then challenged with a mismatched virulent serotype 3 (Sp3) in the lung, which they cannot typically eliminate. Prior exposures to unrelated pneumococci proved protective, with multi-log reductions in lung CFU in mice previously exposed to unrelated pneumococci, compared to vehicle controls. RNAseq analysis of lungs 24h after Sp3 infection revealed an enrichment of lymphocyte-related pathways due to prior pneumococcal exposures, including immunoglobulin and other B cell-related genes (suggesting a local production of antibodies) as well as T helper cell signatures (particularly relating to Th17 cells). Prior to final infection, there were no differences in numbers of B cells or T cells in the lung, and no inflammation in H&E sections. However, ex vivo stimulation of CD4+ T cells revealed such lungs to contain more IL-17A producers, suggesting resident memory. We conclude that serial respiratory infections establish lung resident memory Th17 and B cells that cooperate to protect against pneumonia.
Direct effects of alcohol on the mucosal barrier and the implications on HIV transmission (MUC2P.935)
Authors: Nichols Whitney , Amedee Angela 
Published: January 2023

Abstract
Alcohol abuse is associated with an increased risk of HIV sexual transmission; however, the biological changes in the genital tract are unknown. The first line of defense is provided by the cervicovaginal epithelium acting as a physical barrier to infection. The epithelial cell innate properties are affected by various factors within the genital milieu. We hypothesize that alcohol abuse compromises cervicovaginal epithelial barrier function resulting in enhanced penetration of HIV to the underlying submucosa. Using a vaginal epithelial cell line grown at an air-liquid interface in a transwell, we modeled chronic alcohol exposure by supplementing the basolateral media with physiologically relevant levels of ethanol (50 mM). Epithelium barrier disruption was evident in the alcohol-treated cells by a significant decrease in TEER (p=0.001) and an increased permeability to 10kDa FITC-dextran (p=0.01) relative to control. Cell viability was unaffected by chronic alcohol exposure. Epithelial cells of the female genital tract exhibit significant changes in physical barrier integrity after exposure to intoxicating levels of alcohol. These changes in epithelial cell innate properties provide evidence for a biological mechanism of enhanced HIV penetration and infection in women who abuse alcohol. Future studies in alcohol-exposed cell culture models of both the upper and lower genital mucosa will identify specific mechanisms of HIV transmission.
Mesenchymal stem cells: new directions in treating asthma (THER2P.955)
Authors: Bonfield Tracey , Sutton Morgan , Lennon Donald , Caplan Arnold 
Published: January 2023

Abstract
INTRODUCTION: Mesenchymal stem cells (MSC) therapy has been investigated for inflammatory diseases. We studied MSCs efficacy in the murine model of chronic asthma hypothesizing that MSCs have the capacity to resolve inflammation and remodeling. METHODS: MSCs were administered to the ovalbumin murine model of chronic asthma after sensitization and 3 weeks of challenge. Animals were euthanized 7 days post-MSCs followed by bronchoalveolar lavage (BAL) for total cell count, differentials and cytokines. A separate set of animals were used to evaluate histopathology and markers of remodeling using ImagePro program and insoluble and soluble collagen levels. In vitro cultures of fibroblasts were used to study how MSCs impact remodeling. RESULTS: MSCs decreased weight loss, clinical score, epithelial cell hyperplasia, recruitment of BAL eosinophils, mucins, cytokines and systemic levels of IgE (P&lt;0.05 for each). MSCs decreased soluble (28±6 to 13±9 mg collagen/lung) and insobuble (31±11 to 24±3 mg collagen/lung) collagen levels consistent with our ImagePro quantification. MSCs decreased type I and III collagen expression by 54±11% (n=3, p=0.04) and 30±8% (n=3, p=0.02) respectively. CONCLUSIONS: MSCs decreased airway inflammation and remodeling in the chronic asthma model emphasizing their unique therapeutic potential. ACKNOWLEDGEMENTS: Funded by the George and Virginia Baldwin Fund and American Lung Association: RG-169572.
Aberrant IL-17 production, mediated by SOCS1 deficiency, promotes inflammatory skin pathologies and lymphadenopathy in an IFN gamma independent manner. (THER2P.957)
Authors: Lam Brandon , Armbruster Cristina , Cain Antia , Collins Teresa , Larkin Joseph 
Published: January 2023

Abstract
Although it has been previously reported that mice deficient in SOCS1 develop lupus-like pathologies including skin lesions, the contributing pathogenic mechanisms have not been fully elucidated. We have observed that SOCS1+/- IFNγ-/- mice, but not IFNγ-/-, SOCS1+/-, or wild-type mice develop significant spontaneous skin pathology on the back and ears. The hyperplasia was characterized by significant accumulations of CD3+ T cells, F4/80+ macrophages, and neutrophils. Moreover, SOCS1+/- IFNγ-/- mice presented with lymphadenopathy and splenomegaly. Notably, SOCS1+/- IFNγ-/- leukocytes stimulated with αCD3/αCD28 in vitro were hyper proliferative and produced significant amounts of IL17 and IL-6 compared to IFNy-/- controls. To assess the contribution of excess IL17 production in this overt pathology, SOCS1+/- IFNy-/- mice were treated with IL17 neutralizing antibodies or an IgG control. Strikingly, administration of αIL17 mediated a significant reduction in lymphadenopathy, comparable to IFNγ-/- mice. Moreover, αIL17 treatment significantly reduced dermal leukocyte infiltration and skin lesions compared to SOCS1+/- IFNγ-/- mice receiving IgG control or no treatment. Together, these results present a novel role of SOCS1 in the regulation of IL17 production and subsequent onset of spontaneous skin pathology. Furthermore, these data suggest that amelioration of SOCS1 deficiency using SOCS1 mimetic peptides may have implications in the regulation of inflammatory skin pathologies.
Anthocyanin extracted from black soybean seed coats prevents autoimmune arthritis by suppressing the development of Th17 cells and synthesis of proinflammatory cytokines by such cells, via inhibition of NF-κB (THER3P.972)
Authors: Kim Sung-Min , Min Hong-Ki , Baek Seung-Ye , Woo Jung-Won , Park Jin-Sil , Cho Mi-La , Lee Jennifer , Kwok Seung-Ki , Park Sung-Hwan 
Published: January 2023

Abstract
We investigated the therapeutic effects of anthocyanin extracted from black soybean seed coats (AEBS) in a murine model of collagen-induced arthritis (CIA) and human peripheral blood mononuclear cells (PBMCs), and explored possible mechanisms by which AEBS might exert anti-arthritic effects. A CIA model was induced in DBA/1J mice.. Joints were assessed in terms of arthritis incidence, clinical arthritis scores, and histological features. The extent of oxidative stress in affected joints was determined by measuring the levels of nitrotyrosine and inducible nitric oxide synthase. NF-κB activity was assayed via Western blotting. Osteoclast formation was assessed via TRAP staining. In the CIA model, AEBS decreased the incidence of arthritis, histological inflammation, cartilage scores, and oxidative stress. AEBS reduced the levels of proinflammatory cytokines in affected joints of CIA mice and suppressed NF-κB signaling. AEBS repressed differentiation of Th17 cells and expression of Th17- associated genes in vitro, in both splenocytes of CIA mice and human PBMCs. Tartrate-resistant acid phosphatase+ (TRAP) multinucleated cells fell, in a dose-dependent manner, upon addition of AEBS. The anti-arthritic effects of AEBS were associated with decreases in Th17 cell numbers, and the levels of proinflammatory cytokines synthesized by such cells, mediated via suppression of NF-κB signaling. Additionally, AEBS suppressed osteoclastogenesis and reduced oxidative stress levels.
Blockade of surface bound TGF-β on regulatory T cells abrogates suppression of effector T cell function within the tumor microenvironment (TUM2P.1015)
Authors: Budhu Sadna , Schaer David , Li Yongbiao , Houghton Alan , Silverstein Samuel , Merghoub Taha , Wolchok Jedd 
Published: January 2023

Abstract
Regulatory T cells (Treg) play a role in suppression of anti-melanoma immunity; however, the exact mechanism is poorly understood. Through intravital two photon microcopy, we found that tumor-specific Pmel-1 effectors engage in cell-cell interactions with tumor resident Tregs. To determine if contact between Tregs and Teff hinders killing of tumor cells in vivo, we utilized ex-vivo three-dimensional collagen-fibrin gel cultures of B16 melanoma cells. Collagen-fibrin gel cultures recapitulated the in vivo suppression, rendering the dissociated tumor resistant to killing by in vitro activated antigen specific T cells. In vivo depletion of Tregs in Foxp3-DTR mice prior to tumor excision reversed the suppression. In vivo modulation of Tregs by GITR ligation also reduced the number of intra-tumor Tregs leading to ex-vivo tumor killing. Using neutralizing antibodies, we found that blocking TGF-β reversed the suppression. In addition, soluble factors from collagen-fibrin gel tumors do not inhibit killing suggesting that suppression is contact or proximity dependent. The CD8 T cells recovered from these gels exhibit a decrease in Granzyme B expression and an increase in expression of T cell exhaustion marker PD-1. These findings support the conclusion that intra-tumor contact with Tregs during the effector phase of the immune response is responsible for inhibiting anti-melanoma immunity in a TGF-β dependent manner shedding light into novel ways to inhibit intratumoral Tregs.
A novel monoclonal antibody to the HLA of cisplatin resistant ovarian cancer cells (TUM2P.1018)
Authors: Kaabinejadian Saghar , Patterson Andrea , Bardet Wilfried , Jackson kenneth , Mcmurtrey Curtis , Wichner Timea , Hawkins Oriana , Weidanz Jon , Hildebrand William 
Published: January 2023

Abstract
Cisplatin is widely used as a chemotherapeutic drug in the treatment of ovarian cancer. Resistance to cisplatin occurs in about one-third of women during the primary course of treatment. We hypothesized that the class I HLA of cisplatin-resistant ovarian cancer cells present peptides distinct to these cells as compared to sensitive cells and that HLA/peptide complexes unique to cisplatin-resistant cells would be valuable targets for immunotherapeutic intervention. To identify the peptides that are uniquely presented by cisplatin-resistant ovarian cancer cells, the intrinsic cisplatin-resistant cells (SKOV3) and sensitive cells (A2780, OV90, FHIOSE) were characterized by comparative mass spectrometry. Peptide sequences distinct to cisplatin-resistant cells include a peptide (VMF11) derived from thioredoxin interacting protein (TXNIP) that was in high abundance in SKOV3. Next a T cell receptor mimic monoclonal antibody (RL41A) against A*02:01/VMF11 complex was generated. The specificity and affinity of RL41A toward VMF11/A*02:01 complex was shown by staining peptide-pulsed T2 cells and surface plasmon resonance respectively. Staining of ovarian cancer cells by flow cytometry also demonstrates that RL41A stains cisplatin-resistant cells but not drug sensitive cells. We therefore report the successful development of a monoclonal antibody that represents an attractive candidate for further validation using cisplatin-resistant and sensitive primary ovary tissues.
Induction of robust antitumor immunity by exogenous interleukin-33 (TUM2P.1005)
Authors: Dominguez Donye , Ye Cong , Geng Zhe , chen siqi , Qin Lei , Fan Jie , long alan , Zhang Bin 
Published: January 2023

Abstract
IL-33 is associated with the induction of Th2-type immunity, however it has recently gained attention for its role in boosting Th1-type immunity and CD8+ T cell function. We have discovered that IL-33 can induce robust antitumor effect through a CD8+ T cell dependent mechanism. Systemic administration of recombinant IL-33 (rIL-33) alone was sufficient to inhibit growth of established tumors in multiple mouse tumor models. Notably, rIL-33 treatment promoted antitumor CD8+ T cell expansion and effector function. Mechanistically, rIL-33 therapy primarily and directly targets dendritic cells in tumor bearing mice, thereby restores CTL activity by increasing antigen cross-presentation within the tumor microenvironment. Furthermore, agonist activation of CD40, which is induced by rIL-33 treatment, stabilized and induced regression of established tumors. Our study has elucidated the potential use of rIL-33 as a novel immunotherapy option for the treatment of established cancers.
Devising a glycoantigen specific DC immunotherapy to develop an efficient anti-tumor response within the hypoxic environment of glioblastoma (TUM2P.1026)
Authors: Ginwala Rashida , Sagar Divya , Huang Xiaofang , Foss Catherine , Karakashev Sergey , Khan Zafar , Philip Ramila , Pomper Martin , Reginato Mauricio , Jain Pooja 
Published: January 2023

Abstract
Glioblastoma (GBM) is the most malignant type of brain tumor, its therapy hindered by the hypoxic microenvironment that promotes tumor resistance and inhibits immune cell function. We propose combining dendritic cell (DC) immunotherapy with hypoxia reversal to eradicate GBM. HIF-1α, a transcription factor that stimulates genes promoting angiogenesis and tumor growth, was expressed in both GBM cells and DCs under hypoxia. Hypoxia also downregulated expression of HLA-DR, CD86 and HLA-ABC on DCs affecting their antigen processing and presentation capability in addition to reducing the generation of pro-inflammatory cytokines such as TNF- α and IL-6. In vivo imaging revealed fluorescently labeled DCs migrating away from site of injection into spleen and mediastinal lymph nodes of mice with GBM indicating chemoattraction of DCs to areas of inflammation post hypoxia reversal using using antisense HIF-1α plasmid. In order to identify tumor antigens we used glycan analysis wherein GlcNAc was overexpressed in hypoxic GBM cells. We then enriched GlcNAc expressing glycoantigens and identified 46 glycopeptides derived from 33 glycoproteins. Amongst them Lamb1, SerpinH1, CD63 and others are associated with tumor survival, progression, invasion, immune evasion and therapy resistance. Lectins expressed on DCs complimentary to these glycans will be identified to devise a DC based vaccine, which in conjunction with hypoxia reversal will augment the efficacy of existing therapies against GBM.
A Toll-like receptor (TLR) 5 agonist entolimod mediates anti-metastatic activity via NK cell-dependent T cell activation (TUM2P.1029)
Authors: Brackett Craig , Kojouharov Bojidar , Veith Jean , Greene Kellee , Gollnick Sandra , Burdelya Lyudmila , Abrams Scott , Gudkov Andrei 
Published: January 2023

Abstract
Directing innate immunity against cancer is a promising but poorly developed approach to immunotherapy due to the risk of acute inflammation induced by innate immunity activators. In this regard, TLR5 is a unique innate immune receptor with a distinct tissue specificity of expression and induction of a specific cytokine profile upon activation by its agonist bacterial flagellin that is significantly safer than that induced by other TLR agonists. Entolimod is an optimized Salmonella flagellin derivative with demonstrated safety and efficacy in protecting normal cells from stresses such as radiation or chemotherapy, while not protecting or stimulating tumors. We show here that systemic administration of entolimod has potent antitumor effects in mouse syngeneic colon (CT26) and breast (4T1) cancer models, including suppression of liver metastases and development of CD8 T cell memory. In these models, entolimod treatment leads to blood-borne homing of NK cells to the liver followed by activation of CD4 and CD8 T cells. Antibody-mediated depletion and adoptive transfer experiments showed that all three of these cell types are essential for entolimod’s antitumor effects and demonstrate a pivotal role for NK cell-mediated CD8 and CD4 T cell activation and formation of CD8 T cell memory. Therefore, entolimod has strong promise as a safe, effective and broadly applicable immunotherapeutic agent against liver metastases, which are currently a major cause of cancer-associated mortality.
Un-masking the latent immunogenicity of neoepitopes by checkpoint blockade (TUM2P.1031)
Authors: Hodio Jennifer , Srivastava Pramod 
Published: January 2023

Abstract
Comparison of transcriptome sequences of the BALB/c mouse fibrosarcoma Meth A with the normal BALB/c genome led to identification of 1528 heterozygous tumor-specific point mutations, which, using the NetMHC algorithm, generated 203 Kd-restricted potential neoepitopes1. BALB/c mice were immunized with each of 11 candidate-neoepitopes which had a high binding affinity to Kd (IC50 &lt;500 nM), and were challenged with live Meth A cells. Not a single candidate-neoepitope elicited tumor rejection. Mice were then immunized with the same candidate-neoepitopes in combination with 9D9, an antagonistic antibody to CTLA-4 (mouse anti-mouse IgG2b). In preliminary results, a small number of candidate-neoepitopes that did not elicit tumor rejection on their own appear to be active in tumor rejection, when combined with checkpoint blockade of CTLA-4. These results as well as a mechanistic dissection of this un-covering of latent immunogenicity by checkpoint blockade shall be presented. 1Duan F, Duitama J, Al Seesi S, Ayres CM, Corcelli SA, Pawashe AP, Blanchard T, McMahon D, Sidney J, Sette A, Baker BM, Mandoiu II, Srivastava PK. Genomic and Bioinformatic Profiling of Mutational Neoepitopes Reveals New Rules to Predict Anticancer Immunogenicity." J Exp Med. 211 (2014): 2231-248. PMID: 25245761
Effects of anti-VISTA mAb and its combination therapy in antitumor immunity (TUM2P.1035)
Authors: Kondo Yuta , Ohno Tatsukuni , Azuma Miyuki 
Published: January 2023

Abstract
[Purpose] V-domain Ig suppressor of T-cell activation (VISTA) is a novel immune checkpoint molecule that regulate T-cell activation. VISTA is expressed on both T cells and antigen-presenting cells. In this study, we generated a new mAb against VISTA (MIH63) and examined effects of monotherapy and combined therapy with either CTLA-4 or PD-1 blockade in murine SCCVII and CT26 tumor models. [Results] In a SCCVII tumor model, VISTA was expressed on all TIL and regional lymph node (rLN) T cells, whereas CTLA-4 was selectively induced in all CD8⁺ TIL and LN cells and PD-1 was induced on some T cells. Monotherapy with MIH63 did not clearly affect the growth of SCCVII and CT26, but significantly elevated CD8+ T cell activation assessed by CD25, IFN-g and TNF-a expression. MIH63 significantly reduced the number of CD8+ T cells. Monotherapy of CTLA-4 blockade efficiently reduced the tumor growth and a combination therapy with MIH63 further decreased the tumor growth. Consistently, MIH63 in the combination therapies enhanced CD8+ T cell activation, but decreased the ratio of CD8+ T cells. Blockade of FcγR by 2.4G2 restored the depletion of CD8+ T cells by MIH63, but not the CD8+ T cell activation. [Discussion] Our results suggest that MIH63 mainly acts as an antagonistic mAb to interfere regulatory function of VISTA, but in some part, induce CD8+ T cell-depletion via FcγR-mediated ADCC. The use of non-depleting anti-VISTA mAb may develop more effective results in the VISTA blockade.