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Myeloid regulatory cells

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https://www.readbyqxmd.com/read/28722110/renal-infiltrating-cd11c-cells-are-pathogenic-in-murine-lupus-nephritis-through-promoting-cd4-t-cell-responses
#1
Xiaofeng Liao, Jingjing Ren, Alec Reihl, Tharshikha Pirapakaran, Bharath Sreekumar, Thomas E Cecere, Christopher M Reilly, Xin M Luo
Lupus nephritis (LN) is a major manifestation of systemic lupus erythematosus (SLE) causing morbidity and mortality in 40-60% of SLE patients. The pathogenic mechanisms of LN are not completely understood. Recent studies have demonstrated the presence of various immune cell populations in lupus nephritic kidneys of both SLE patients and lupus-prone mice. These cells may play important pathogenic or regulatory roles in situ to promote or sustain LN. Here, using lupus-prone mouse models, we showed the pathogenic role of a kidney-infiltrating CD11c(+) myeloid cell population in LN...
July 19, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28721449/role-of-regulatory-t-cells-in-acute-myeloid-leukemia-patients-undergoing-relapse-preventive-immunotherapy
#2
Frida Ewald Sander, Malin Nilsson, Anna Rydström, Johan Aurelius, Rebecca E Riise, Charlotta Movitz, Elin Bernson, Roberta Kiffin, Anders Ståhlberg, Mats Brune, Robin Foà, Kristoffer Hellstrand, Fredrik B Thorén, Anna Martner
Regulatory T cells (Tregs) have been proposed to dampen functions of anti-neoplastic immune cells and thus promote cancer progression. In a phase IV trial (Re:Mission Trial, NCT01347996, http://www.clinicaltrials.gov ) 84 patients (age 18-79) with acute myeloid leukemia (AML) in first complete remission (CR) received ten consecutive 3-week cycles of immunotherapy with histamine dihydrochloride (HDC) and low-dose interleukin-2 (IL-2) to prevent relapse of leukemia in the post-consolidation phase. This study aimed at defining the features, function and dynamics of Foxp3(+)CD25(high)CD4(+) Tregs during immunotherapy and to determine the potential impact of Tregs on relapse risk and survival...
July 18, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28716080/pretreatment-antigen-specific-immunity-and-regulation-association-with-subsequent-immune-response-to-anti-tumor-dna-vaccination
#3
Laura E Johnson, Brian M Olson, Douglas G McNeel
BACKGROUND: Immunotherapies have demonstrated clinical benefit for many types of cancers, however many patients do not respond, and treatment-related adverse effects can be severe. Hence many efforts are underway to identify treatment predictive biomarkers. We have reported the results of two phase I trials using a DNA vaccine encoding prostatic acid phosphatase (PAP) in patients with biochemically recurrent prostate cancer. In both trials, persistent PAP-specific Th1 immunity developed in some patients, and this was associated with favorable changes in serum PSA kinetics...
July 18, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28715505/the-clinical-and-immunological-performance-of-28-days-survival-model-of-cecal-ligation-and-puncture-in-humanized-mice
#4
Krzysztof Laudanski, Natalia Lapko, Mateusz Zawadka, Benjamin X Zhou, Gwenn Danet-Desnoyers, George S Worthen
Sepsis triggers a coordinated and thorough immune system response with long-term unfavorable sequelae after the initial insult. Long-term recovery from sepsis has garnered increasing attention recently, but a lack of suitable animal models impairs progress in this area. Our study, therefore, aimed to address the performance of the immune system in a survivable model of sepsis (cecal ligation and sepsis; CLP) for up to 28 d after the initial injury in humanized mice. Our model mimics human sepsis with weight loss and post-sepsis hypothermia...
2017: PloS One
https://www.readbyqxmd.com/read/28711922/hmgb1-promotes-myeloid-derived-suppressor-cells-and-renal-cell-carcinoma-immune-escape
#5
Jinfeng Li, Jiajia Sun, Ruiming Rong, Long Li, Wenjun Shang, Dongkui Song, Guiwen Feng, Feifei Luo
Despite high immunogenicity and marked presence of immune cells in the RCC(renal cell carcinoma), immunotherapy fails to develop effective anti-tumor immune responses. This is due to the negative regulatory factors in the tumor microenvironment. As the main contributor of immunosuppression, myeloid-derived suppressor cells (MDSCs) inhibited anti-tumor immunity and promoted tumor progression. Meanwhile, it is confirmed that high mobility group box-1 protein (HMGB1) shows a high expression in many solid tumors and HMGB1 with high expression is involved in tumor immune escape...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28704840/hype-or-hope-the-prognostic-value-of-infiltrating-immune-cells-in-cancer
#6
Tristan A Barnes, Eitan Amir
Interactions between immune and malignant cells have been known to have clinical relevance for decades. The potential for immune control is now being therapeutically enhanced with checkpoint inhibitors and other novel agents to improve outcomes in cancer. The importance of the immune infiltrate as a prognostic marker is increasingly relevant. In this minireview, we present an overview of the immune infiltrate and its spatial organisation, and summarise the prognostic value of immune cells in different cancer types...
July 13, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28698173/interferon-regulatory-factor-5-controls-necrotic-core-formation-in-atherosclerotic-lesions-by-impairing-efferocytosis
#7
Anusha N Seneviratne, Andreas O Edsfeldt, Jennifer E Cole, Christina Kassiteridi, Maarten Swart, Inhye Park, Patricia Green, Tariq E Khoyratty, David G Saliba, Michael E Goddard, Stephen N Sansom, Isabel Goncalves, Rob Krams, Irina A Udalova, Claudia Monaco
Background -Myeloid cells are central to atherosclerotic lesion development and vulnerable plaque formation. Impaired ability of arterial phagocytes to uptake apoptotic cells (efferocytosis), promotes lesion growth and establishment of a necrotic core. The transcription factor Interferon Regulatory Factor (IRF)-5 is an important modulator of myeloid function and programming. We sought to investigate whether IRF5 affects the formation and phenotype of atherosclerotic lesions. Methods -We investigated the role of IRF5 in atherosclerosis in two complementary models...
July 11, 2017: Circulation
https://www.readbyqxmd.com/read/28693523/inhibition-of-lin28b-impairs-leukemia-cell-growth-and-metabolism-in-acute-myeloid-leukemia
#8
Jianbiao Zhou, Chonglei Bi, Ying Qing Ching, Jing-Yuan Chooi, Xiao Lu, Jessie Yiying Quah, Sabrina Hui-Min Toh, Zit-Liang Chan, Tuan Zea Tan, Phyllis Sy Chong, Wee-Joo Chng
BACKGROUND: Current conventional chemotherapy for acute myeloid leukemia (AML) can achieve remission in over 70% of patients, but a majority of them will relapse within 5 years despite continued treatment. The relapse is postulated to be due to leukemia stem cells (LSCs), which are different from normal hematopoietic stem cells (HSCs). LIN28B is microRNA regulator and stem cell reprogramming factor. Overexpression of LIN28B has been associated with advance human malignancies and cancer stem cells (CSCs), including AML...
July 11, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28689651/frequencies-of-peripheral-immune-cells-in-older-adults-following-seasonal-influenza-vaccination-with-an-adjuvanted-vaccine
#9
David Goldeck, Heidi Theeten, Fakhri Hassouneh, Lilly Oettinger, Kilian Wistuba-Hamprecht, Nathalie Cools, Ourania E Tsitsilonis, Graham Pawelec
As age increases, immune responses and consequently protection following vaccination to seasonal influenza is commonly believed to decrease. Possible drivers of this immune dysfunction include immunosenescence, repeated exposure to the same seasonal influenza antigens, and prior infection with cytomegalovirus (CMV). Here, to determine immune parameters distinguishing vaccine humoral responders (R) from non-responders (NR) following vaccination, we surveyed broad peripheral blood "cellular immune correlates" of older adults vaccinated with Fluad® (an adjuvanted subunit influenza vaccine containing strains H1N1, H3N2 and B)...
July 6, 2017: Vaccine
https://www.readbyqxmd.com/read/28689360/regulatory-myeloid-cells-an-underexplored-continent-in-b-cell-lymphomas
#10
REVIEW
Mikael Roussel, Jonathan M Irish, Cedric Menard, Faustine Lhomme, Karin Tarte, Thierry Fest
In lymphomas arising from the germinal center, prognostic factors are linked to the myeloid compartment. In particular, high circulating monocyte or myeloid-derived suppressor cell counts are associated with poor prognosis for patients with high-grade B-cell lymphomas. Macrophages with an M2 phenotype are enriched within lymphoma tumors. However, the M1/M2 nomenclature is now deprecated and the clinical impact of this phenotype remains controversial. Across cancer types, myeloid cells are primarily thought to function as immune suppressors during tumor initiation and maintenance, but the biological mechanisms behind the myeloid signatures are still poorly understood in germinal center B-cell lymphomas...
July 8, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28689001/immuno-oncologic-approaches-car-t-cells-and-checkpoint-inhibitors
#11
REVIEW
Francesca Gay, Mattia D'Agostino, Luisa Giaccone, Mariella Genuardi, Moreno Festuccia, Mario Boccadoro, Benedetto Bruno
Advances in understanding myeloma biology have shown that disease progression is not only the consequence of intrinsic tumor changes but also of interactions between the tumor and the microenvironment in which the cancer grows. The immune system is an important component of the tumor microenvironment in myeloma, and acting on the immune system is an appealing new treatment strategy. There are 2 ways to act toward immune cells and boost antitumor immunity: (1) to increase antitumor activity (acting on T and NK cytotoxic cells), and (2) to reduce immunosuppression (acting on myeloid-derived stem cells and T regulatory cells)...
June 17, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28680747/arginase-inhibition-suppresses-lung-metastasis-in-the-4t1-breast-cancer-model-independently-of-the-immunomodulatory-and-anti-metastatic-effects-of-vegfr-2-blockade
#12
Chiara Secondini, Oriana Coquoz, Lorenzo Spagnuolo, Thibaud Spinetti, Sanam Peyvandi, Laura Ciarloni, Francesca Botta, Carole Bourquin, Curzio Rüegg
Tumor angiogenesis promotes tumor growth and metastasis. Anti-angiogenic therapy in combination with chemotherapy is used for the treatment of metastatic cancers, including breast cancer but therapeutic benefits are limited. Mobilization and accumulation of myeloid-derived suppressor cells (MDSC) during tumor progression and therapy have been implicated in metastasis formation and resistance to anti-angiogenic treatments. Here, we used the 4T1 orthotopic syngenic mouse model of mammary adenocarcinoma to investigate the effect of VEGF/VEGFR-2 axis inhibition on lung metastasis, MDSC and regulatory T cells (Tregs)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28680381/exacerbation-of-japanese-encephalitis-by-cd11c-hi-dendritic-cell-ablation-is-associated-with-an-imbalance-in-regulatory-foxp3-and-il-17-cd4-th17-cells-and-in-ly-6c-hi-and-ly-6c-lo-monocytes
#13
Jin Young Choi, Jin Hyoung Kim, Ajit Mahadev Patil, Seong Bum Kim, Erdenebelig Uyangaa, Ferdaus Mohd Altaf Hossain, Seong Kug Eo
Japanese encephalitis (JE) is neuroinflammation characterized by uncontrolled infiltration of peripheral leukocytes into the central nervous system (CNS). We previously demonstrated exacerbation of JE following CD11c(hi) dendritic cell (DC) ablation in CD11c-DTR transgenic mice. Moreover, CD11c(hi) DC ablation led to abnormal differentiation of CD11b(+)Ly-6C(hi) monocytes and enhanced permeability of the blood-brain barrier (BBB), resulting in promoting the progression of JE. Here, we examined changes in lymphoid and myeloid-derived leukocyte subpopulations associated with pro- and anti-inflammation during JE progression...
June 2017: Immune Network
https://www.readbyqxmd.com/read/28679535/small-molecule-based-inhibition-of-mek1-2-proteins-dampens-inflammatory-responses-to-malaria-reduces-parasite-load-and-mitigates-pathogenic-outcomes
#14
Xianzhu Wu, Kiran K Dayanand, Ramesh P Thylur, Christopher C Norbury, D Channe Gowda
Malaria infections cause several systemic and severe single or multi-organ pathologies, killing hundreds of thousands of people annually. Considering the existing widespread resistance of malaria parasites to antiparasitic drugs and their high propensity to develop drug resistance, alternative strategies are required to manage malaria infections. Since malaria is a host immune response-driven disease, one approach is based on gaining a detailed understanding of the molecular and cellular processes that modulate malaria-induced innate and adaptive immune responses...
July 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28674082/intratumoral-sting-activation-with-t-cell-checkpoint-modulation-generates-systemic-antitumor-immunity
#15
Casey R Ager, Matthew J Reilley, Courtney Nicholas, Todd Bartkowiak, Ashvin R Jaiswal, Michael A Curran
Coordinated manipulation of independent immune regulatory pathways in the tumor microenvironment - including blockade of T-cell checkpoint receptors and reversal of suppressive myeloid programs - can render aggressive cancers susceptible to immune rejection. Elevated toxicity associated with combination immunotherapy, however, prevents translation of the most efficacious regimens. We evaluated T-cell checkpoint modulating antibodies targeting CTLA-4, PD-1, and 4-1BB together with myeloid agonists targeting either STING or Flt3 in the TRAMP-C2 model of prostate cancer to determine whether low-dose intratumoral delivery of these agents could elicit systemic control of multi-focal disease...
July 3, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28668887/frequency-of-myeloid-derived-suppressor-cells-in-the-peripheral-blood-reflects-the-status-of-tumor-recurrence
#16
Tomoko Tanaka, Mitsugu Fujita, Hiroshi Hasegawa, Akira Arimoto, Masayasu Nishi, Eiji Fukuoka, Yutaka Sugita, Takeru Matsuda, Yasuo Sumi, Satoshi Suzuki, Yoshihiro Kakeji, Kimihiro Yamashita
BACKGROUND: Malignant tumors inhibit antitumor immune responses, which are driven by T-regulatory cells or myeloid-derived suppressor cells (MDSCs). Since MDSCs are involved in invasion, migration, and metastasis of tumor cells, we hypothesized that MDSCs are also involved in tumor recurrence after surgical resection. MATERIALS AND METHODS: C57BL/6 mice were subcutaneously inoculated with B16F10 melanoma cells in the right flank. In some experiments, established tumors were surgically resected...
July 2017: Anticancer Research
https://www.readbyqxmd.com/read/28666264/antitumor-immunity-induced-by-ve-cadherin-modified-dc-vaccine
#17
Jing Zhou, Yufeng Xi, Xiyan Mu, Rongce Zhao, Hongdou Chen, Li Zhang, Yang Wu, Qiu Li
Dendritic cells (DCs) are the most potent antigen-presenting cells. A strong interest has been developed in DC vaccines for cancer immunotherapy. Besides, angiogenesis is essential for tumor growth. VE-cadherin has a crucial function in various aspects of vascular biological functions. Here, we produced the full VE-cadherin gene modified DC vaccine (DC-VEC). Its antitumor immunity and chief mechanism driving antitumor effect was evaluated. Analyses were performed including test of antitumor antibody, CTL-mediated cytotoxicity experiment, vascular density, evaluation of the variation of cells and cytokines in immunoregulation...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28666258/peptide-microarray-profiling-identifies-phospholipase-c-gamma-1-plc-%C3%AE-1-as-a-potential-target-for-t-8-21-aml
#18
Hasan Mahmud, Frank J G Scherpen, Tiny Meeuwsen de Boer, Harm-Jan Lourens, Caroline Schoenherr, Matthias Eder, Michaela Scherr, Victor Guryev, Eveline S De Bont
The t(8;21) (q22;q22) chromosomal translocation is one of the most frequent genetic alterations in acute myeloid leukemia (AML) which has a need for improved therapeutic strategies. We found PLC-γ1 as one of the highest phosphorylated peptides in t(8;21) AML samples compared to NBM or CN-AML in our previous peptide microarray. PLC-γ1 is known to play a role in cancer progression, however, the impact of PLC-γ1 in AML is currently unknown. Therefore, we aimed to study the functional role of PLC-γ1 by investigating the cellular growth, survival and its underlying mechanism in t(8;21) AML...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28659358/b-cell-extrinsic-myd88-and-fcer1g-negatively-regulate-autoreactive-and-normal-b-cell-immune-responses
#19
Rebecca A Sweet, Kevin M Nickerson, Jaime L Cullen, Yujuan Wang, Mark J Shlomchik
MyD88 and FcR common γ-chain (Fcer1g, FcRγ) elicit proinflammatory responses to exogenous Ags. Deletion of these receptors in autoimmune models has generally led to reduced overall disease. In B cells, Myd88 is required for anti-DNA and anti-RNA autoantibody responses, whereas Fcer1g is not expressed in these cells. The roles of these receptors in myeloid cells during B cell autoimmune activation remain less clear. To investigate the roles of Myd88 and Fcer1g in non-B cells, we transferred anti-self-IgG (rheumatoid factor) B cells and their physiologic target Ag, anti-chromatin Ab, into mice lacking Fcer1g, Myd88, or both and studied the extrafollicular plasmablast response...
June 28, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28659048/blocking-the-vista-pathway-enhances-disease-progression-in-nzb%C3%A2-%C3%A3-%C3%A2-nzw-f1-female-mice
#20
P A Sergent, S F Plummer, J Pettus, R Mabaera, J K DeLong, D A Pechenick, C M Burns, R J Noelle, S Ceeraz
V-domain Ig suppressor of T-cell activation (VISTA) is a critical negative checkpoint molecule involved in regulating the immune response. Targeting the pathway with an antagonist anti-VISTA antibody designated 13F3 has been shown to enhance disease severity in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. To determine if VISTA plays a role in murine lupus, New Zealand Black × New Zealand White (BWF1) mice were treated with 13F3 or control hamster Ig and disease monitored...
January 1, 2017: Lupus
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