scholarly journals 654 Analysis of IDO-1 expression on dendritic cells and factors influencing its up- and downregulation in pancreatic cancer

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A683-A683
Author(s):  
Michael Hollingsworth ◽  
Kamiya Mehla ◽  
Kirsten Eberle ◽  
Ying Huang ◽  
Aleata Triplett ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Immune Response ◽  
T Cells ◽  
Dendritic Cells ◽  
Rna Sequencing ◽  
Immune Cells ◽  
Systemic Immunosuppression ◽  
Tumor Bearing ◽  
Factors Influencing ◽  
Tolerogenic Dcs

BackgroundPancreatic Ductal Adenocarcinoma (PDAC) is bad. An immunosuppressive tumor microenvironment (TME) with an excess of immunosuppressive immune cells and cytokine/chemokine factors contribute to local and systemic immunosuppression in PDAC.1 Our laboratory has generated single-cell RNA-Sequencing (scRNA-Seq.) data from spleens derived from PDAC patients and healthy counterparts. This data demonstrates the existence of dendritic cell (DC) subsets with a tolerogenic phenotype. These DCs display increased expression of several markers, including Indoleamine 2,3-dioxygenases (IDO-1 and IDO-2), widely accepted as markers for a specific population of DCs: tolerogenic DCs. These cells evoke an immunosuppressive signal leading to activation of regulatory T cells and MDSCs as well as apoptosis of CD8+ and CD4+ effector T cells.2 3MethodsTo validate our scRNA-Seq. data, we performed pilot investigations harvesting DCs from the spleen of PDAC patients and healthy subjects. Besides examining human specimens, we also investigated the IDO-1 expression on splenic DCs from tumor-bearing mice, orthotopically implanted with LSL-KrasG12D; LSL-Trp53R172H/+; Pdx1-Cre (KPC)-derived cell lines. It is known that tumor-derived exosomes can impact DC-differentiation to a tolerogenic phenotype.4 Exosome purification using differential ultracentrifugation is a well-established method in our lab and optimized for our autopsy samples. We analyzed tumor-derived exosomes for their potential in modulating IDO-1 expression on DCs in in vitro assays. Briefly, we incubated DCs with different exosome concentrations and harvested the cells for RNA-sequencing and flow cytometry.ResultsCompared to normal spleens, DCs from PDAC spleens displayed higher expression of IDO-1 (figure 1). Additionally, KPC-tumor-bearing mice showed higher expression of IDO-1 on DCs from the spleen and blood compared to wild-type mice. Further investigating the influence of PDAC-derived exosomes on marker expression on DCs have shown an apparent increase in expression of IDO-1 when culturing splenic-derived DCs with tumor-derived exosomes (figure 2).ConclusionsWhile tolerogenic DCs are essential in regulating the homeostasis between immune response and immune tolerance,5 several studies have shown IDO-1 overexpression in cancer. Investigating tolerogenic DCs is an essential part of our lab's efforts to understand the nature of the immune response in PDAC. Future directions for this project include determining molecular pathways that regulate the expression of IDO-1. Additionally, we will investigate downstream mechanisms through which exosomes modulate the switch to a tolerogenic phenotype. We also plan to further characterize different splenic DC populations by evaluating their interplay with other immune cells in the context of antigen-specificity and other factors influencing these cells' properties.ReferencesMundry CS, Eberle KC, Singh PK, Hollingsworth MA, Mehla K. Local and systemic immunosuppression in pancreatic cancer: targeting the stalwarts in tumor's arsenal. BBA - Reviews on Cancer 2020;1874(1):188387.Liu M, Wang X, Wang L, Ma X, Gong Z, Zhang S, Li Y. Targeting the IDO1 pathway in cancer: from bench to bedside. Journal of Hematology & Oncology 2018;11(1):100.Hornyák L, Dobos N, Koncz G, Karányi Z, Páll D, Szabó Z, Halmos G, Székvölgyi L. The role of Indoleamine-2,3-Dioxygenase in cancer development, diagnostics, and therapy. Frontiers in immunology 2018;9:1.Bronte V, Pittet MJ. The spleen in local and systemic regulation of immunity. Immunity 2013;39(5):806–818.Domogalla MP, Rostan PV, Raker VK, Steinbrink K. Tolerance through education: how tolerogenic dendritic cells shape immunity. Frontiers in Immunology 2017;8:1764.Ethics ApprovalThis study was approved by the University of Nebraska Medical Center Ethics Board; approval numbers IRB#: 440-16-EP and IRB#: 091-01.Abstract 654 Figure 1Expression of IDO-1 and IDO-2 on DCs from PDAC spleen (blue) .and normal spleen (orange)Abstract 654 Figure 2Change in expression of IDO-1 through treatment of DCs with different concentrations of tumor-derived exosomes

scholarly journals IMPACT OF TUMOR-DERIVED FACTORS ON DENDRITIC CELLS IN CANCER

2017 ◽  
Vol 16 (1) ◽  
pp. 12-23 ◽  
Author(s):  
A. A. Keskinov ◽  
M. R. Shurin ◽  
V. M. Bukhman ◽  
Z. S. Shprakh
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Dendritic Cells ◽  
Dendritic Cell ◽  
Tumor Microenvironment ◽  
Cancer Patients ◽  
Immune Cells ◽  
Humoral Immune ◽  
Cell Mediated Immune Response ◽  
Immune Response To Cancer

Dendritic cells play key role during tumorigenesis and immune response to it. They are able to uptake and present antigens to T cells, resulting in specific T cell mediated immune response. Furthermore, interaction between dendritic cells and other types of immune cells may boost cell-mediated and humoral immune response to cancer. Contrary to that, numerous tumor-derived factors may attract dendritic cells to neoplastic sites, causing impairment of their maturation, differentiation, and functional activity, resulting in deficiency of anti-tumor immune response or dendritic cell-mediated tolerance. Various factors within tumor microenvironment may either stimulate or inhibit dendritic cells and therefore need to be determined for improving efficacy of biotherapy utilizing dendritic cells. Meanwhile, recovery of dendritic cells functions in cancer patients remains one of primary aims for cancer immunotherapy. This review outlines main types of tumor-derived factors and their impact on dendritic cells in cancer.

scholarly journals Donor Macrophages Modulate Rejection after Heart Transplantation

2021 ◽  
Author(s):  
Benjamin Kopecky ◽  
Hao Dun ◽  
Junedh Amrute ◽  
Chieh-Yu Lin ◽  
Andrea Bredemeyer ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Dendritic Cells ◽  
Single Cell ◽  
Rna Sequencing ◽  
Innate Immune ◽  
Allograft Survival ◽  
Cell Ablation ◽  
Single Cell Rna Sequencing ◽  
Cellular Rejection

Background: Cellular rejection after heart transplantation imparts significant morbidity and mortality. Current immunosuppressive strategies are imperfect, target recipient T-cells, and have a multitude of adverse effects. The innate immune response plays an essential role in the recruitment and activation of T-cells. Targeting the donor innate immune response would represent the earliest interventional opportunity within the immune response cascade. There is limited knowledge regarding donor immune cell types and functions in the setting of cardiac transplantation and no current therapeutics exist for targeting these cell populations. Methods: Using genetic lineage tracing, cell ablation, and conditional gene deletion, we examined donor mononuclear phagocyte diversity and function during acute cellular rejection of transplanted hearts in mice. We performed single cell RNA sequencing on donor and recipient macrophages, dendritic cells, and monocytes at multiple timepoints after transplantation. Based on our single cell RNA sequencing data, we evaluated the functional relevance of donor CCR2+ and CCR2- macrophages using selective cell ablation strategies in donor grafts prior to transplant. Finally, perform functional validation of our single cell derived hypothesis that donor macrophages signal through MYD88 to facilitate cellular rejection. Results: Donor macrophages persisted in the transplanted heart and co-existed with recipient monocyte-derived macrophages. Single-cell RNA sequencing identified donor CCR2+ and CCR2- macrophage populations and revealed remarkable diversity amongst recipient monocytes, macrophages, and dendritic cells. Temporal analysis demonstrated that donor CCR2+ and CCR2- macrophages were transcriptionally distinct, underwent significant morphologic changes, and displayed unique activation signatures after transplantation. While selective depletion of donor CCR2- macrophages reduced allograft survival, depletion of donor CCR2+ macrophages prolonged allograft survival. Pathway analysis revealed that donor CCR2+ macrophages were being activated through MYD88/NF-κβ signaling. Deletion of MYD88 in donor macrophages resulted in reduced antigen presenting cell recruitment, decreased emergence of allograft reactive T-cells, and extended allograft survival. Conclusions: Distinct populations of donor and recipient macrophages co-exist within the transplanted heart. Donor CCR2+ macrophages are key mediators of allograft rejection and inhibition of MYD88 signaling in donor macrophages is sufficient to suppress rejection and extend allograft survival. This highlights the therapeutic potential of donor heart-based interventions.

scholarly journals The immune response of T cells and therapeutic targets related to regulating the levels of T helper cells after ischaemic stroke

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Tian-Yu Lei ◽  
Ying-Ze Ye ◽  
Xi-Qun Zhu ◽  
Daniel Smerin ◽  
Li-Juan Gu ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
Immune Responses ◽  
Ischaemic Stroke ◽  
Immune Cells ◽  
Tissue Injury ◽  
Recovery Period ◽  
Vital Functions ◽  
Anti Inflammatory

AbstractThrough considerable effort in research and clinical studies, the immune system has been identified as a participant in the onset and progression of brain injury after ischaemic stroke. Due to the involvement of all types of immune cells, the roles of the immune system in stroke pathology and associated effects are complicated. Past research concentrated on the functions of monocytes and neutrophils in the pathogenesis of ischaemic stroke and tried to demonstrate the mechanisms of tissue injury and protection involving these immune cells. Within the past several years, an increasing number of studies have elucidated the vital functions of T cells in the innate and adaptive immune responses in both the acute and chronic phases of ischaemic stroke. Recently, the phenotypes of T cells with proinflammatory or anti-inflammatory function have been demonstrated in detail. T cells with distinctive phenotypes can also influence cerebral inflammation through various pathways, such as regulating the immune response, interacting with brain-resident immune cells and modulating neurogenesis and angiogenesis during different phases following stroke. In view of the limited treatment options available following stroke other than tissue plasminogen activator therapy, understanding the function of immune responses, especially T cell responses, in the post-stroke recovery period can provide a new therapeutic direction. Here, we discuss the different functions and temporal evolution of T cells with different phenotypes during the acute and chronic phases of ischaemic stroke. We suggest that modulating the balance between the proinflammatory and anti-inflammatory functions of T cells with distinct phenotypes may become a potential therapeutic approach that reduces the mortality and improves the functional outcomes and prognosis of patients suffering from ischaemic stroke.

scholarly journals 453 Novel combination immunotherapy for boosting and priming immune responses in pancreatic cancer: strong anti-tumour effects with interleukin-15 and CD40 agonist treatment

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A480-A480
Author(s):  
Jonas Van Audenaerde ◽  
Elly Marcq ◽  
Bianca von Scheidt ◽  
Ashleigh Davey ◽  
Amanda Oliver ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
T Cells ◽  
Dendritic Cells ◽  
Natural Killer ◽  
Mouse Models ◽  
Cd8 T Cells ◽  
Tumour Growth ◽  
Immune Memory ◽  
Combination Immunotherapy ◽  
Interleukin 15

BackgroundWith the poorest 5-year survival of all cancers, improving treatment for pancreatic cancer is one of the biggest challenges in cancer research. In this era of combination immunotherapies, we sought to explore the potential of combining both priming and activation of the immune system. To achieve this, we combined a CD40 agonist with interleukin-15 and tested its potential in pancreatic cancer.MethodsTwo different mouse models of pancreatic cancer were used to assess the potential of this combination regimen. Therefore, effects on tumour growth kinetics and survival were charted. Differential effects on immune signatures was investigated using RNA sequencing. Functional immune subset involvement was tested using different immune depletion experiments and multicolour flow cytometry in different relevant immune sites. Immune memory was checked using re-challenge experiments.ResultsWe demonstrated profound reduction in tumour growth and increased survival of mice with the majority of mice being cured when both agents were combined, including an unprecedented dose reduction of CD40 agonist without losing any efficacy (fig 1). RNA sequencing analysis showed involvement of natural killer cell and T cell mediated anti-tumour responses and the importance of antigen-presenting cell pathways. This combination resulted in enhanced infiltration of tumours by both cytotoxic T cells and natural killer cells, as well as a striking increase in the ratio of CD8+ T cells over T regulatory cells. We also observed a significant increase in numbers of dendritic cells in tumour draining lymph nodes, particularly CD103+ dendritic cells with cross-presentation potential. A critical role for CD8+ T cells and involvement of natural killer cells in the anti-tumour effect was highlighted. Importantly, strong immune memory was established, with an increase in memory CD8+ T cells only when both interleukin-15 and the CD40 agonist were combined.Abstract 453 Figure 1Tumour kinetics and survival in Panc02 (left) and KPC (right) pancreatic cancer mouse modelsConclusionsWe demonstrated profound synergistic anti-tumour effects upon combination of CD40 agonist and interleukin-15 treatment in mouse models of pancreatic cancer. This preclinical data supports initiation of a first-in-human clinical trial with this combination immunotherapy strategy in pancreatic cancer.

scholarly journals Cell subtypes and immune dysfunction in peritoneal fluid of endometriosis revealed by single-cell RNA-sequencing

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gen Zou ◽  
Jianzhang Wang ◽  
Xinxin Xu ◽  
Ping Xu ◽  
Libo Zhu ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Single Cell ◽  
Natural Killer ◽  
Rna Sequencing ◽  
Peritoneal Cavity ◽  
Immune Cells ◽  
Peritoneal Fluid ◽  
Control Sample ◽  
Immune Dysfunction ◽  
Single Cell Rna Sequencing

Abstract Background Endometriosis is a refractory and recurrent disease and it affects nearly 10% of reproductive-aged women and 40% of infertile patients. The commonly accepted theory for endometriosis is retrograde menstruation where endometrial tissues invade into peritoneal cavity and fail to be cleared due to immune dysfunction. Therefore, the comprehensive understanding of immunologic microenvironment of peritoneal cavity deserves further investigation for the previous studies mainly focus on one or several immune cells. Results High-quality transcriptomes were from peritoneal fluid samples of patients with endometriosis and control, and firstly subjected to 10 × genomics single-cell RNA-sequencing. We acquired the single-cell transcriptomes of 10,280 cells from endometriosis sample and 7250 cells from control sample with an average of approximately 63,000 reads per cell. A comprehensive map of overall cells in peritoneal fluid was first exhibited. We unveiled the heterogeneity of immune cells and discovered new cell subtypes including T cell receptor positive (TCR+) macrophages, proliferating macrophages and natural killer dendritic cells in peritoneal fluid, which was further verified by double immunofluorescence staining and flow cytometry. Pseudo-time analysis showed that the response of macrophages to the menstrual debris might follow the certain differentiation trajectory after endometrial tissues invaded into the peritoneal cavity, that is, from antigen presentation to pro-inflammation, then to chemotaxis and phagocytosis. Our analyses also mirrored the dysfunctions of immune cells including decreased phagocytosis and cytotoxic activity and elevated pro-inflammatory and chemotactic effects in endometriosis. Conclusion TCR+ macrophages, proliferating macrophages and natural killer dendritic cells are firstly reported in human peritoneal fluid. Our results also revealed that immune dysfunction happens in peritoneal fluid of endometriosis, which may be responsible for the residues of invaded menstrual debris. It provided a large-scale and high-dimensional characterization of peritoneal microenvironment and offered a useful resource for future development of immunotherapy.

scholarly journals Adipocyte, Immune Cells, and miRNA Crosstalk: A Novel Regulator of Metabolic Dysfunction and Obesity

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1004
Author(s):  
Sonia Kiran ◽  
Vijay Kumar ◽  
Santosh Kumar ◽  
Robert L Price ◽  
Udai P. Singh
Keyword(s):  
Insulin Resistance ◽  
Immune Response ◽  
T Cells ◽  
Immune Cells ◽  
Metabolic Diseases ◽  
Liver Disorder ◽  
Low Grade ◽  
Peripheral Tissues ◽  
Nonalcoholic Fatty Liver ◽  
Cytokines And Chemokines

Obesity is characterized as a complex and multifactorial excess accretion of adipose tissue (AT) accompanied with alterations in the immune response that affects virtually all age and socioeconomic groups around the globe. The abnormal accumulation of AT leads to several metabolic diseases, including nonalcoholic fatty liver disorder (NAFLD), low-grade inflammation, type 2 diabetes mellitus (T2DM), cardiovascular disorders (CVDs), and cancer. AT is an endocrine organ composed of adipocytes and immune cells, including B-Cells, T-cells and macrophages. These immune cells secrete various cytokines and chemokines and crosstalk with adipokines to maintain metabolic homeostasis and low-grade chronic inflammation. A novel form of adipokines, microRNA (miRs), is expressed in many developing peripheral tissues, including ATs, T-cells, and macrophages, and modulates the immune response. miRs are essential for insulin resistance, maintaining the tumor microenvironment, and obesity-associated inflammation (OAI). The abnormal regulation of AT, T-cells, and macrophage miRs may change the function of different organs including the pancreas, heart, liver, and skeletal muscle. Since obesity and inflammation are closely associated, the dysregulated expression of miRs in inflammatory adipocytes, T-cells, and macrophages suggest the importance of miRs in OAI. Therefore, in this review article, we have elaborated the role of miRs as epigenetic regulators affecting adipocyte differentiation, immune response, AT browning, adipogenesis, lipid metabolism, insulin resistance (IR), glucose homeostasis, obesity, and metabolic disorders. Further, we will discuss a set of altered miRs as novel biomarkers for metabolic disease progression and therapeutic targets for obesity.

scholarly journals Murine Myeloid Dendritic Cells That Phagocytose Apoptotic T Cells Inhibit the Immune Response via NO

PLoS ONE ◽  
2012 ◽  
Vol 7 (11) ◽  
pp. e49378 ◽  
Author(s):  
Kaili Zhong ◽  
Wengang Song ◽  
Qian Wang ◽  
Chao Wang ◽  
Xi Liu ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Dendritic Cells ◽  
Myeloid Dendritic Cells

scholarly journals 873 Pharmacologic macrophage depletion affects metastasis formation by modulating systemic immune responses in a genetic pancreatic cancer model

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A926-A926
Author(s):  
Heidi Griesmann ◽  
Heidi Griesmann ◽  
Heidi Griesmann ◽  
Christof Drexel ◽  
Nada Milosevic ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
T Cells ◽  
Regulatory T Cells ◽  
Mouse Model ◽  
Immune Cells ◽  
Tumour Progression ◽  
Metastasis Formation ◽  
Macrophage Depletion ◽  
Genetic Mouse Model ◽  
Liposomal Clodronate

BackgroundTumour-associated macrophages (TAM) play an important role in mediating tumour progression. In pancreatic cancer, infiltrating macrophages have been identified not only in invasive tumours, but also in early preinvasive pancreatic intraepithelial neoplasias and are known to mediate tumour progression.MethodsWe aimed to study the impact of pharmacological macrophage depletion by liposomal clodronate in the genetic mouse model of pancreatic cancer (KPC mouse: LSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-Cre). KPC mice were treated with liposomal clodronate or control liposomes from week 8 to week 20. Tumour and metastasis formation as well as alterations in local and circulating immune cells and cytokines were analysed.ResultsTreatment with liposomal clodronate effectively reduced CD11b-positive macrophages both in the pancreas and other organs such as liver, lung and spleen. Tumour incidence and size was only slightly reduced. However, metastasis formation in the liver und lungs was markedly diminished after macrophage depletion. Reduced macrophage count was associated with significant alterations in circulating growth factors and mediators known to be secreted by macrophages and associated with angiogenesis, most prominently VEGF. Moreover, application of liposomal clodronate led to marked alterations in circulating immune cells, among them reduced regulatory T cells.ConclusionsPharmacological depletion of macrophages in a genetic mouse model of pancreatic cancer markedly reduced metastasis formation and is associated with modulated profile of both secreted mediators and regulatory T cells. Pharmacological modulation of infiltrating macrophages represents a promising avenue for antimetastatic therapeutic approaches.

scholarly journals 839 Microbiota-specific T follicular helper cells drive tertiary lymphoid structure formation and anti-tumor immunity in colorectal cancer

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A880-A880
Author(s):  
Abigail Overacre-Delgoffe ◽  
Hannah Bumgarner ◽  
Anthony Cillo ◽  
Ansen Burr ◽  
Justin Tometich ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
T Cells ◽  
Tumor Immunity ◽  
Cell Response ◽  
Tumor Burden ◽  
T Cell Response ◽  
Tumor Bearing ◽  
Follicular Helper ◽  
Necessary And Sufficient

BackgroundColorectal cancer (CRC) is one of the most common and deadly cancers in the US, and the survival rate for advanced cases is poor. While immunotherapy has revolutionized cancer treatment, CRC remains largely unresponsive, with only ~6% of patients responding to anti-PD1. Specific microbiome signatures are associated with anti-PD1 response in melanoma patients; however, the underlying mechanism remains unclear. While the microbiome in cancer patients has been extensively studied, the endogenous immune response to these microbes and the subsequent effects on cancer immunity remain unstudied. Most microbes reside within the gut, and bacteria that adhere to the intestinal epithelium can stimulate bacteria-specific immune responses. Therefore, we hypothesized that the microbiome, especially adherent, immunogenic bacteria, may support anti-tumor immunity through activation of local microbiota-specific T cells.MethodsUsing a carcinogen-induced mouse model of CRC, we sought to determine the impact of microbiome modulation on the anti-tumor immune response. We colonized tumor-bearing mice with Helicobacter hepaticus (Hhep) and assessed tumor burden, survival, and immune infiltration. Lymphocytes were isolated from the tumor and surrounding tissue when tumors were terminal (12 weeks). We utilized TCR transgenic mice and MHC class II tetramers to track the spatial and transcriptional Hhep-specific T cell response through 5’ single cell RNAseq, flow cytometry, and spectral immunofluorescence.ResultsHhep colonization in tumor-bearing mice led to decreased tumor burden and significantly improved survival. Interestingly, colonization induced activation of Hhep-specific T follicular helper cells (TFHs) that supported formation of mature peri- or intra-tumoral tertiary lymphoid structures (TLS). The presence of TLS led to increased infiltration of cytotoxic lymphocytes (T and NK cells) within the tumor core. Surprisingly, the anti-tumor response was dependent on CD4+ T and B cells but not CD8+ T cells. Using TFH KO mice, we found that Hhep-specific CD4+ T cells were both necessary and sufficient to drive TLS maturation and anti-tumor immunity.ConclusionsHere, we demonstrate that addition of a single bacterial species after tumor formation leads to a reduction in CRC tumor burden and increased survival through TLS maturation. This microbiome-dependent remodeling of the tumor microenvironment is driven by Hhep-specific TFH cells that are both necessary and sufficient for tumor control, demonstrating for the first time that microbiota-specific T cells contribute to anti-tumor immunity. Overall, these findings suggest that microbiome modulation and the subsequent microbiota-specific CD4+ T cell response may represent a new variety of immunotherapies for cancers that remain resistant to checkpoint blockade.

scholarly journals ILDR1 Is a Prognostic Biomarker and Associated With Immune Infiltration in Gastric Cancer

2021 ◽  
Author(s):  
Yanling Ma ◽  
WenBo Qi ◽  
BaoHong Gu ◽  
XueMei Li ◽  
ZhenYu Yin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Dendritic Cells ◽  
Cancer Patients ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
Copy Number ◽  
Sequencing Data ◽  
Number Variation ◽  
Gastric Cancer Patients

Abstract Objective: To investigate the association between ILDR1 and prognosis and immune infiltration in gastric cancer. Methods: We analyzed the RNA sequencing data of 9736 tumor tissues and 8587 normal tissues in the TCGA and GTEx databases through the GEPIA2 platform. The expression of ILDR1 in gastric cancer and normal gastric mucosa tissues with GEPIA and TIMER. Clinical subgroup analysis was made through Kaplan-Meier analysis. Analyzed the correlation between ILDR1 and VEGFA expression in gastric cancer, through the gene sequencing data of gastric cancer in TCGA. Explored the relationship between ILDR1 methylation and the prognosis of gastric cancer patients through the MethSurv database. The correlation between ILDR1 and immune cells and the correlation of copy number variation were explored through the TIMER database. Results: ILDR1-high GC patients had a lower PFS and OS. High ILDR1 expression was significantly correlated with tumor grade. There was a negative correlation between the ILDR1 expression and the abundances of CD8+ T, Macrophages and DC and etc. The methylation level of ILDR1 is associated with a good prognosis of gastric cancer. ILDR1 copy number variation was correlated with immune cells, IDLR1 arm-loss was associated with the infiltration of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells, and arm-duplication was associated with the infiltration of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells. Conclusion: The increased expression of ILDR1 is associated with poor prognosis in patients with gastric cancer. ILDR1 can be used as a novel predictive biomarker to provide a new therapeutic target for gastric cancer patients.

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