A comprehensive analysis of TDO2 expression in immune cells and characterization of immune cell phenotype in TDO2 knockout mice

2021 ◽  
Author(s):  
Susu Li ◽  
Siyu Li ◽  
Yingjie Zhao ◽  
Bingjie Zhang ◽  
Xinwei Wang ◽  
...  
Keyword(s):  
Immune Cells ◽  
Knockout Mice ◽  
Immune Cell ◽  
Comprehensive Analysis ◽  
Cell Phenotype

scholarly journals Immune cell-specific Cre reporter mouse labels a subset of CNS neurons

2019 ◽  
Author(s):  
Aurélie Bouteau ◽  
Botond Z. Igyártó
Keyword(s):  
Immune Cells ◽  
Langerhans Cells ◽  
Immune Cell ◽  
Neuronal Marker ◽  
Reporter Mouse ◽  
Cns Neurons ◽  
The Central Nervous System ◽  
Antigen Presenting

AbstractHuLangerin-Cre-YFPf/f mice were generated to specifically mark a subset of antigen presenting immune cells, called Langerhans cells (LCs). During histological characterization of these mice, we found that, in addition to LCs an uncharacterized cell population in the central nervous system (CNS) also expressed YFP. In this study, we found that the CNS YFP+ cells were negative for microglia and astrocyte markers, but they expressed mature neuronal marker NeuN and showed neuronal localization/morphology. Thus, these mice might be used to study the ontogeny, migration and the role of a subset of CNS neurons.

scholarly journals Succinate Is an Inflammation-Induced Immunoregulatory Metabolite in Macrophages

Metabolites ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 372 ◽  
Author(s):  
Karl J. Harber ◽  
Kyra E. de Goede ◽  
Sanne G. S. Verberk ◽  
Elisa Meinster ◽  
Helga E. de Vries ◽  
...  
Keyword(s):  
Immune Responses ◽  
Immune Cells ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Cell Phenotype ◽  
Independent Manner ◽  
Inflammatory Macrophages ◽  
Necrosis Factor

Immunometabolism revealed the crucial role of cellular metabolism in controlling immune cell phenotype and functions. Macrophages, key immune cells that support progression of numerous inflammatory diseases, have been well described as undergoing vast metabolic rewiring upon activation. The immunometabolite succinate particularly gained a lot of attention and emerged as a crucial regulator of macrophage responses and inflammation. Succinate was originally described as a metabolite that supports inflammation via distinct routes. Recently, studies have indicated that succinate and its receptor SUCNR1 can suppress immune responses as well. These apparent contradictory effects might be due to specific experimental settings and particularly the use of distinct succinate forms. We therefore compared the phenotypic and functional effects of distinct succinate forms and receptor mouse models that were previously used for studying succinate immunomodulation. Here, we show that succinate can suppress secretion of inflammatory mediators IL-6, tumor necrosis factor (TNF) and nitric oxide (NO), as well as inhibit Il1b mRNA expression of inflammatory macrophages in a SUCNR1-independent manner. We also observed that macrophage SUCNR1 deficiency led to an enhanced inflammatory response without addition of exogenous succinate. While our study does not reveal new mechanistic insights into how succinate elicits different inflammatory responses, it does indicate that the inflammatory effects of succinate and its receptor SUCNR1 in macrophages are clearly context dependent.

scholarly journals Diverse homeostatic and immunomodulatory roles of immune cells in the developing mouse lung at single cell resolution

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Racquel Domingo-Gonzalez ◽  
Fabio Zanini ◽  
Xibing Che ◽  
Min Liu ◽  
Robert C Jones ◽  
...  
Keyword(s):  
Postnatal Development ◽  
Immune Cells ◽  
Immune Cell ◽  
Mouse Lung ◽  
Cell Phenotype ◽  
Physical Interaction ◽  
Early Postnatal Development ◽  
Hypoxic Environment ◽  
Context Specific ◽  
Air Liquid Interface

At birth, the lungs rapidly transition from a pathogen-free, hypoxic environment to a pathogen-rich, rhythmically distended air-liquid interface. Although many studies have focused on the adult lung, the perinatal lung remains unexplored. Here, we present an atlas of the murine lung immune compartment during early postnatal development. We show that the late embryonic lung is dominated by specialized proliferative macrophages with a surprising physical interaction with the developing vasculature. These macrophages disappear after birth and are replaced by a dynamic mixture of macrophage subtypes, dendritic cells, granulocytes, and lymphocytes. Detailed characterization of macrophage diversity revealed an orchestration of distinct subpopulations across postnatal development to fill context-specific functions in tissue remodeling, angiogenesis, and immunity. These data both broaden the putative roles for immune cells in the developing lung and provide a framework for understanding how external insults alter immune cell phenotype during a period of rapid lung growth and heightened vulnerability.

scholarly journals Immune Cell Profiling of Peripheral Blood as Signature for Response During Checkpoint Inhibition Across Cancer Types

2021 ◽  
Vol 11 ◽  
Author(s):  
Vinicius Araujo B. de Lima ◽  
Morten Hansen ◽  
Iben Spanggaard ◽  
Kristoffer Rohrberg ◽  
Sine Reker Hadrup ◽  
...  
Keyword(s):  
Immune Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Large Fraction ◽  
Response To Treatment ◽  
Cell Phenotype ◽  
Checkpoint Inhibition ◽  
Color Flow ◽  
Immune Profile

Despite encouraging results with immune checkpoint inhibition (ICI), a large fraction of cancer patients still does not achieve clinical benefit. Finding predictive markers in the complexity of the tumor microenvironment is a challenging task and often requires invasive procedures. In our study, we looked for putative variables related to treatment benefit among immune cells in peripheral blood across different tumor types treated with ICIs. For that, we included 33 patients with different solid tumors referred to our clinical unit for ICI. Peripheral blood mononuclear cells were isolated at baseline, 6 and 20 weeks after treatment start. Characterization of immune cells was carried out by multi-color flow cytometry. Response to treatment was assessed radiologically by RECIST 1.1. Clinical outcome correlated with a shift towards an effector-like T cell phenotype, PD-1 expression by CD8+T cells, low levels of myeloid-derived suppressor cells and classical monocytes. Dendritic cells seemed also to play a role in terms of survival. From these findings, we hypothesized that patients responding to ICI had already at baseline an immune profile, here called ‘favorable immune periphery’, providing a higher chance of benefitting from ICI. We elaborated an index comprising cell types mentioned above. This signature correlated positively with the likelihood of benefiting from the treatment and ultimately with longer survival. Our study illustrates that patients responding to ICI seem to have a pre-existing immune profile in peripheral blood that favors good outcome. Exploring this signature can help to identify patients likely to achieve benefit from ICI.

scholarly journals IMMU-27. ANALYSIS OF IMMUNE SIGNATURES IN PEDIATRIC GLIOBLASTOMAS FOR PATIENT STRATIFICATION TO IMMUNOTHERAPY

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii365-iii365
Author(s):  
Vidyalakshmi Chandramohan ◽  
Tyler Evangelous ◽  
Eric S Lipp ◽  
Bhavna Hora ◽  
Darell D Bigner ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tumor Cells ◽  
Immune Cells ◽  
Median Overall Survival ◽  
Immune Cell ◽  
Cell Mass ◽  
Cell Phenotype ◽  
Patient Stratification ◽  
Rna Seq ◽  
Selection Of

Abstract BACKGROUND Pediatric glioblastoma (pGBM), despite being relatively rare (incidence rate: 0.5/100,000), are a leading cause of cancer deaths in children with a median overall survival of 9–15 months. In recent years, immunotherapy has emerged as one of the more promising advances in oncology, with impressive response rates reported in several malignancies. Effective application of immunotherapy in brain tumors depends upon a better understanding of the immune cell phenotype and mechanisms of immunosuppression in these tumors. This understanding will allow for the selection of patient population who are most likely to benefit from immunotherapeutic approaches. MATERIAL AND METHODS In order to determine the frequency, distribution, and phenotype of tumor-infiltrating immune cells in pGBMs, we undertook an immunohistochemical survey on 19 recurrent pGBMs for CD3, CD8, CD4, CD163, PD-1, PD-L1, and FoxP3; RNA-Seq was also performed on a subset of 9 cases. Distribution of lymphocytes (LYMPHS) was recorded as intratumoral (IT) or perivascular (PV). RESULTS The analysis indicates intratumoral CD3+ LYMPHS are commonly <5% of tumor cell mass; however, approximately half (10/19) of these recurrent pGBM have infiltrates that range from 5 to 30% CD3+ LYMPHS. Of these, 4/10 CD3+ tumors exhibit brisk CD8+ infiltrates that are associated with PD-L1+ tumor cells. These tumors with brisk CD3+/CD8+ LYMPHS and PD-L1+ tumor cells were associated with longer survivals. The data were confirmed by RNA-seq analysis. CONCLUSION PD-L1+ pGBMs associated with CD3+/CD8+ LYMPH infiltrates deserve further investigation as candidates for immunotherapy.

scholarly journals In Situ Characterization of Human Lymphoid Tissue Immune Cells by Multispectral Confocal Imaging and Quantitative Image Analysis; Implications for HIV Reservoir Characterization

2021 ◽  
Vol 12 ◽  
Author(s):  
Eirini Moysi ◽  
Perla M. Del Rio Estrada ◽  
Fernanda Torres-Ruiz ◽  
Gustavo Reyes-Terán ◽  
Richard A. Koup ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Immune Cells ◽  
Cd4 T Cells ◽  
Lymphoid Tissue ◽  
Immune Cell ◽  
Hiv Reservoir ◽  
Human Lymphoid Tissue

CD4 T cells are key mediators of adaptive immune responses during infection and vaccination. Within secondary lymphoid organs, helper CD4 T cells, particularly those residing in germinal centers known as follicular helper T cells (Tfh), provide critical help to B-cells to promote their survival, isotype switching and selection of high affinity memory B-cells. On the other hand, the important role of Tfh cells for the maintenance of HIV reservoir is well documented. Thus, interrogating and better understanding the tissue specific micro-environment and immune subsets that contribute to optimal Tfh cell differentiation and function is important for designing successful prevention and cure strategies. Here, we describe the development and optimization of eight multispectral confocal microscopy immunofluorescence panels designed for in depth characterization and immune-profiling of relevant immune cells in formalin-fixed paraffin-embedded human lymphoid tissue samples. We provide a comprehensive library of antibodies to use for the characterization of CD4+ T-cells -including Tfh and regulatory T-cells- as well as CD8 T-cells, B-cells, macrophages and dendritic cells and discuss how the resulting multispectral confocal datasets can be quantitatively dissected using the HistoCytometry pipeline to collect information about relative frequencies and immune cell spatial distributions. Cells harboring actively transcribed virus are analyzed using an in-situ hybridization assay for the characterization of HIV mRNA positive cells in combination with additional protein markers (multispectral RNAscope). The application of this methodology to lymphoid tissues offers a means to interrogate multiple relevant immune cell targets simultaneously at increased resolution in a reproducible manner to guide CD4 T-cell studies in infection and vaccination.

scholarly journals 671 Biological impacts of standard of care chemotherapies on immune effector cells from AML patients

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A699-A699
Author(s):  
Dmitry Zhigarev ◽  
Alexander MacFarlane ◽  
Christina Drenberg ◽  
Reza Nejati ◽  
Asya Varshavsky ◽  
...  
Keyword(s):  
Nk Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Cell Phenotype ◽  
Second Line ◽  
Color Flow ◽  
Immune Effector ◽  
Effector Cells ◽  
Immune Effector Cells ◽  
And Function

BackgroundAcute myeloid leukemia (AML) is a heterogeneous group of malignant bone marrow diseases, characterized by massive and uncontrolled proliferation of myeloid precursor cells, which alters normal blood cell ratios. This disease is common to older adults and collectively displays one of the lowest 5-year overall survival rates (<25%) among all cancers, currently representing the deadliest form of leukemia. Improved treatments are clearly needed, and immunotherapies are attractive candidate therapies to explore.There are currently several standard chemotherapeutic treatment schemes for AML, which could be divided into two major groups: (1) cytotoxic chemotherapy (“7+3” or daunorubicin-cytarabine) and (2) hypomethylating agents (HMAs). HMAs include both 5-azacytidine and decitabine, which are cytidine analogs that inhibit DNA methyltransferase, resulting in the hypomethylation of DNA and inducing expression of silenced gene loci. Currently, HMAs are routinely delivered in combination with the Bcl-2 inhibitor venetoclax.The goals of this study are to determine how these standard first line therapies can affect the frequency and functional integrity of effector immune cells in patients' blood and establish when the phenotype and function of immune cells are restored to identify time windows when second line immunotherapies could be most effective.MethodsMore than 100 blood samples were obtained from 33 previously untreated AML patients. More than 50 measurable biomarkers were analyzed using 14-color flow cytometry to assess immune phenotypes of T and NK cells in peripheral blood of AML patients prior to treatment and at up to four timepoints after initiation of treatment with HMA or chemotherapy.ResultsWe found several significant changes in immune cell phenotype and function that occur in response to these therapies. Treatment with HMAs was strikingly less impactful on immune cells in patients compared to previously published in vitro studies. Nevertheless, HMA treatment increased perforin levels in T and NK cells, inhibited IFN-gamma secretion by CD8+ T cells, and changed expression of several checkpoint molecules. While chemotherapy caused fewer phenotypic changes it dramatically decreased the total number of immune cells. We also determined viable, functional and phenotypical recovery periods for immune effector cells after the treatments.ConclusionsOur results are important for introducing new second line immunotherapies to these chemotherapeutic regimens for treating AML and to improve overall understanding of immune cell behavior under conditions of anti-tumor treatment.AcknowledgementsSupported by grants from Janssen and the U.S./Israel Binational Science Foundation.Ethics ApprovalThe study was approved by the Fox Chase Cancer Center Institutional Review Board, approval number 17-8010, and all patients provided informed consent before taking part in the study.

scholarly journals Geospatial characterization of immune cell distributions and dynamics across the microenvironment in renal cell carcinoma

2021 ◽  
Author(s):  
Nicholas Chakiryan ◽  
Youngchul Kim ◽  
Anders Berglund ◽  
Gregory Kimmel ◽  
Andrew Chang ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Clinical Stage ◽  
Tumor Stroma ◽  
Imaging Analysis ◽  
Cancer Specific Survival ◽  
Stromal Compartment

Abstract We performed multiplex immunofluorescence (mIF) using an array of myeloid and lymphoid markers on primary tumor samples from 122 patients with RCC. Regions of interest (ROIs) were selected from three distinct tumor zones: the tumor-core, stroma, and tumor-stroma interface. Digital pathologic imaging analysis was leveraged to quantify the geospatial location and distribution of immune cells within the TIME, and these findings were correlated with a variety of tumor molecular profiles. For patients with ccRCC, as clinical stage increased, immunosuppressive M2-like CD163+ TAMs migrated from the tumor compartment and into the stroma at the tumor-stroma interface and became increasingly co-localized with CD8+ T-cells. Furthermore, high CD163+ TAM clustering into the stromal compartment and high CD8+/CD163+ stromal co-localization were independently associated with worse OS and cancer-specific survival (CSS), while accounting for clinical stage. Overall, this data suggests that the pro-tumor effect of M2-like TAMs and their effect on CD8+ T-cells may be dependent on their specific geospatial location and distribution within the TIME -- namely, that M2-like TAMs exert their pro-tumor effect and interact with CD8+ T-cells most effectively from the stromal compartment at the tumor-stroma interface.

scholarly journals Comprehensive Analysis of Immune-Related Metabolic Genes in Lung Adenocarcinoma

2021 ◽  
Author(s):  
Fangfang Li ◽  
Chun Huang ◽  
Llingxiao Qiu ◽  
Ping Li ◽  
Guojun Zhang
Keyword(s):  
Lung Cancer ◽  
Regression Analysis ◽  
Lung Adenocarcinoma ◽  
Immune Cells ◽  
Immune Cell ◽  
Comprehensive Analysis ◽  
Lasso Regression ◽  
Cell Functions ◽  
Qrt Pcr ◽  
Metabolic Genes

Abstract Purpose The immunotherapy of lung adenocarcinoma has received more and more attention. Different immune cells can affect other metabolic genes and lifespan, and cell metabolism directly regulates immune cell functions. Therefore, it is crucial to explore the role of immune-related metabolic genes in lung adenocarcinoma. Methods In this study, we divided immune-related metabolic genes into three categories based on different immune characteristics and researched immune and clinical pathology. LASSO regression analysis was used to screen immune-related metabolic genes, and a clinical prediction model of the screened genes was constructed. Finally, we selected the intersection of immune metabolism genes that are highly expressed in the tumor site and immune metabolism genes that are negatively related to survival, and used qRT-PCR for experimental verification. Results We first screened out immune-related metabolic genes that may affect lung cancer tumor progression, and screened out 9 pivot genes (TK1, TCN1, CAV1, ACMSD, HS3ST2, HS3ST5, AMN, ADRA2C, ACOXL) through LASSO regression analysis and constructed Prognosis model. Finally, through the screening of tumor-related immune metabolism genes, we obtained five pivot genes (HMMR, PFKP, RRM2, TCN1 and TK1). Our qRT-PCR results also show that RRM2 is positively correlated with CDK2, CDK4, CDK6, and CDK8, revealing the close relationship between RRM2 and immune cell tumor infiltration. Conclusion We conducted a comprehensive analysis of the immune infiltration of the tumor microenvironment of lung cancer, and finally determined RRM2 as a promising immune metabolism checkpoint for lung adenocarcinoma based on the high correlation of RRM2 with immune cells and CDK family.

scholarly journals Analysis of Therapeutic Targets and Prognostic Biomarkers of CXC Chemokines in Cervical Cancer Microenvironment

2021 ◽  
Author(s):  
Wei na Kong ◽  
Gang Zhao ◽  
Hai xia Chen ◽  
Wei na Wang ◽  
Xiao qian Shang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Immune Cells ◽  
Immune Cell ◽  
Cell Activity ◽  
Comprehensive Analysis ◽  
Prognostic Biomarkers ◽  
Quantitative Real Time Pcr ◽  
Cell Transport ◽  
Selection Of

Abstract Background: It is well known that the tumor microenvironment (TME) has been received an increasing number of attention. CXC chemokines could regulate immune cell transport and tumor cell activity, thus exerting anti-tumor immunity. However, studies on the expression and prognosis of CXC chemokines in cervical cancer (CC) are more limited. Methods: The study investigated the role of CXC chemokines in the TME and prognosis of CC using public databases. Moreover, quantitative real-time PCR (Q-PCR) and immunohistochemistry (IHC) of CXC chemokines were performed to further verify. Results: The transcriptional levels of CXCL1/3/5/6/8/9/10/11/13/14/16/17 in CC tissues were significantly elevated while the transcriptional levels of CXCL2/4/7/12 were significantly reduced. We reached a consistent conclusion that the expression of CXCL9/10/11/13 was verified by Q-PCR and IHC. Moreover, CC patients with low transcriptional levels of CXCL1/2/3/4/5/8 were signifi-cantly associated with longer overall survival (OS). Our data suggest that RELA, NFKB1, and SP1 are key transcription factors for CXC chemokines, and the LCK, LYN and PAK are CXC chemokine kinases targets. We found significant correlations among the expression of CXC chemokines and the infiltration of six types of immune cells. Conclusions: We performed a comprehensive analysis of CXC chemokines via clinical data and some online tumor database. Our results may provide new idea for the selection of immunotherapeutic targets and prognostic biomarkers for cervical cancer.

Sign in / Sign up

Export Citation Format

Share Document