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Treg cyclophosphamide

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https://www.readbyqxmd.com/read/28855352/low-dose-cyclophosphamide-induces-anti-tumor-t-cell-responses-which-associate-with-survival-in-metastatic-colorectal-cancer
#1
Martin J Scurr, Tom Pembroke, Anja Bloom, David J Roberts, Amanda Thomson, Kathryn Smart, Hayley Bridgeman, Richard A Adams, Alison E Brewster, Robert Jones, Sarah Gwynne, Daniel Blount, Richard Harrop, Robert Hills, Awen Gallimore, Andrew Godkin
PURPOSE: Anti-cancer T-cell responses can control tumors, but immune-suppressive mechanisms in vivo prevent their function. The role of regulatory T-cells (Tregs) in metastatic colorectal cancer (mCRC) is unclear. We have previously shown depletion of Tregs enhances CRC-specific effector T-cell responses. Low dose cyclophosphamide (CPM) targets Tregs in animal models and some human studies, however the effect of CPM in mCRC is unknown. EXPERIMENTAL DESIGN: Fifty-five mCRC patients were enrolled onto a phase I/II trial and randomized to receive two week-long courses of low-dose (50mg twice-a-day) CPM or not...
August 29, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28802588/t-cell-costimulation-blockade-promotes-transplantation-tolerance-in-combination-with-sirolimus-and-post-transplantation-cyclophosphamide-for-haploidentical-transplantation-in-children-with-severe-aplastic-anemia
#2
Sarita Rani Jaiswal, Prakash Bhakuni, Shamsuz Zaman, Satish Bansal, Priyanka Bharadwaj, Sneh Bhargava, Suparno Chakrabarti
We conducted a pilot study employing extended T cell costimulation blockade (COSBL) with Abatacept along with sirolimus and post-transplantation cyclophosphamide (PTCy) in 10 patients (median age 12) with severe aplastic anemia (SAA). Nine patients engrafted in the COSBL group, compared to all 10 patients (median 14 vs 13days) treated on PTCy protocols without abatacept (CONTROL group). The incidence of acute graft-versus-host disease (GVHD) was 10.5% in the COSBL group compared to 50% in the CONTROL group (p=0...
August 9, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28713366/intratumoral-lentivector-mediated-tgf-%C3%AE-1-gene-downregulation-as-a-potent-strategy-for-enhancing-the-antitumor-effect-of-therapy-composed-of-cyclophosphamide-and-dendritic-cells
#3
Joanna Rossowska, Natalia Anger, Agnieszka Szczygieł, Jagoda Mierzejewska, Elżbieta Pajtasz-Piasecka
Vaccination with dendritic cells (DCs) stimulated with tumor antigens can induce specific cellular immune response that recognizes a high spectrum of tumor antigens. However, the ability of cancer cells to produce immunosuppressive factors drastically decreases the antitumor activity of DCs. The main purpose of the study was to improve the effectiveness of DC-based immunotherapy or chemoimmunotherapy composed of cyclophosphamide (CY) and DCs by application of lentivectors (LVs)-encoding short hairpin RNA specific for TGF-β1 (shTGFβ1 LVs)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28655853/rapamycin-alleviates-inflammation-and-muscle-weakness-while-altering-the-treg-th17-balance-in-a-rat-model-of-myasthenia-gravis
#4
Feng Jing, Fei Yang, Fang Cui, Zhao Hui Chen, Li X Ling, Xu S Huang
Myasthenia gravis (MG) is an autoimmune disease commonly treated with immunosuppressants. We evaluated the novel immunosuppressant, rapamycin (RAPA), in a rat model of experimental autoimmune MG (EAMG). Mortality rates in the RAPA (12%) was significantly down compared to the EAMG (88%) or CTX (68%) intervention groups. Muscular weakness decreased after both RAPA and cyclophosphamide (CTX) treatment; however, Lennon scores were lower (1.74 ± 0.49, 3.39 ± 0.21, and 3.81 ± 0.22 in RAPA, CTX, and EAMG groups, respectively), and body weights (203...
June 27, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28645781/immunomodulatory-mechanism-of-bushen-huoxue-recipe-alleviates-cyclophosphamide-induced-diminished-ovarian-reserve-in-mouse-model
#5
Cong Huang, Kunkun Song, Wenwen Ma, Jiahui Ding, Zhuo Chen, Mingmin Zhang
ETHNOPHARMACOLOGICAL RELEVANCE: Bushen Huoxue recipe (BHR) is a Chinese herbal prescription composed of ten herbs and it is widely used for the treatment of diminished ovarian reserve (DOR). This study investigates the potentially beneficial effects and underlying mechanism of BHR on a cyclophosphamide (CTX) induced model of DOR in mice. MATERIALS AND METHODS: Granules of BHR were first subjected to high performance liquid chromatography (HPLC) to determine the exact ingredients within the mixture...
June 21, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28639416/persistently-low-lymphocyte-counts-after-fcr-therapy-for-chronic-lymphocytic-leukemia-are-associated-with-longer-overall-survival
#6
Erel Joffe, N Ariela Arad, Osnat Bairey, Riva Fineman, Rosa Ruchlemer, Naomi Rahimi-Levene, Lev Shvidel, Uri Greenbaum, Ariel Aviv, Tamar Tadmor, Andrei Braester, Neta Goldschmidt, Aaron Polliack, Yair Herishanu
Decreased absolute lymphocyte counts (ALCs) following frontline therapy for chronic lymphocytic leukemia may be associated with disease control, even in patients without evidence of minimal residual disease. We studied the prognostic significance of ALCs during the first year following treatment with fludarabine, cyclophosphamide, and rituximab (FCR). We evaluated 99 patients who achieved a partial response without lymphocytosis (<4.0 × 10(3) cells/μL) or better after FCR. Absolute lymphocyte counts were recorded at 3-, 6-, 9-, and 12-month posttreatment and correlated with overall survival (OS) and event-free survival (EFS)...
June 22, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28619045/human-adipose-derived-mesenchymal-stem-cells-alleviate-obliterative-bronchiolitis-in-a-murine-model-via-ido
#7
Guoping Zheng, Guanguan Qiu, Menghua Ge, Jianping He, Lanfang Huang, Ping Chen, Wei Wang, Qi Xu, Yaoqin Hu, Qiang Shu, Jianguo Xu
BACKGROUND: Long-term survival of lung transplantation is hindered by the development of obliterative bronchiolitis (OB). Adipose-derived stem cells (ASCs) were documented to have more potent immunosuppressive ability than mesenchymal stem cells (MSCs) from bone marrow and placenta. The goal of our study is to evaluate the effect of repeated administration of ASCs on OB and the involvement of indoleamine 2,3-dioxygenase (IDO) mediating the protective effect of ASCs in a heterotopic tracheal transplantation (HTT) model...
June 15, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28454585/modulatory-role-of-regulatory-t-cells-in-a-murine-model-of-severe-equine-asthma
#8
Claudio Henríquez, Gabriel Morán, Cristian Carrasco, José Sarmiento, Miguel Barría, Hugo Folch, Benjamin Uberti
BACKGROUND: It is accepted that T regulatory cells (Treg) control different types of immune responses. In connection with this role, we have recently described an important increase in CD4+, CD25(high), Foxp3+ lymphocytes in the airway system of horses coursing with an exacerbation of severe equine asthma (EA). To explore the potential role of this population in the resolution of EA inflammation, we used a murine experimental model in which airway neutrophilic inflammation, which is similar to that observed in EA, is induced in mice by continual exposure to Aspergillus fumigatus contaminated hay...
April 28, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28351935/bidirectional-immune-tolerance-in-nonmyeloablative-mhc-mismatched-bmt-for-murine-%C3%AE-thalassemia
#9
Shuyu E, Aman Seth, Peter Vogel, Matt Sommers, Taren Ong, Asha B Pillai
Nonmyeloablative conditioning using total lymphoid irradiation (TLI) and rabbit antithymocyte serum (ATS) (the murine preclinical equivalent of antithymocyte globulin [ATG]) facilitates immune tolerance after bone marrow transplantation (BMT) across major histocompatibility complex (MHC) disparities and may be a useful strategy for nonmalignant disorders. We previously reported that donor effector T-cell function and graft-versus-host disease (GVHD) are regulated via recipient invariant natural killer T-cell (iNKT) interleukin-4-driven expansion of donor Foxp3(+) naturally occurring regulatory T cells (Tregs)...
June 1, 2017: Blood
https://www.readbyqxmd.com/read/28131632/cd56-enriched-donor-cell-infusion-after-post-transplantation-cyclophosphamide-for-haploidentical-transplantation-of-advanced-myeloid-malignancies-is-associated-with-prompt-reconstitution-of-mature-natural-killer-cells-and-regulatory-t-cells-with-reduced-incidence
#10
Sarita Rani Jaiswal, Shamsur Zaman, Murugaiyan Nedunchezhian, Aditi Chakrabarti, Prakash Bhakuni, Margoob Ahmed, Kanika Sharma, Sheh Rawat, Paul O'donnell, Suparno Chakrabarti
We conducted a pilot study on the feasibility of CD56-enriched donor cell infusion after post-transplantation cyclophosphamide (PTCy) for 10 patients with advanced myeloid malignancies undergoing haploidentical peripheral blood stem cell transplantation with cyclosporine alone as graft-versus-host disease (GVHD) prophylaxis and compared the outcome and immune reconstitution with a control group of 20 patients undergoing the same without CD56-enriched donor cell infusion. An early and rapid surge of mature NK cells as well as CD4(+) T cells and regulatory T cells (Tregs) was noted compared with the control group...
April 2017: Cytotherapy
https://www.readbyqxmd.com/read/28004985/cyclophosphamide-enhances-anti-tumor-effects-of-a-fibroblast-activation-protein-%C3%AE-based-dna-vaccine-in-tumor-bearing-mice-with-murine-breast-carcinoma
#11
Qiu Xia, Fei Geng, Fang-Fang Zhang, Chen-Lu Liu, Ping Xu, Zhen-Zhen Lu, Yu Xie, Bo Sun, Hui Wu, Bin Yu, Wei Kong, Xiang-Hui Yu, Hai-Hong Zhang
Cyclophosphamide (CY) is a DNA alkylating agent, which is widely used with other chemotherapy drugs in the treatment of various types of cancer. It can be used not only as a chemotherapeutic but also as an immunomodulatory agent to inhibit IL-10 expression and T regulatory cells (Tregs). Fibroblast activation protein α (FAPα) is expressed in cancer-associated fibroblasts in the tumor microenvironment. Immunotherapy based on FAPα, as a tumor stromal antigen, typically induces specific immune response targeting the tumor microenvironment...
February 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/27859243/effect-of-infusion-of-monoclonal-antibodies-to-tumour-necrosis-factor-receptor-super-family-25-on-graft-rejection-in-allo-immune-mice-receiving-autologous-marrow-transplantation
#12
Reginald M Gorczynski, Hassan Sadozai, Fang Zhu, Ismat Khatri
Significant barriers to transplantation exist for individuals who are pre-sensitized to donor antigen and have high titres of donor-reactive antibody. We report the effect of autologous bone marrow transplantation (BMTx) after myeloablation in pre-sensitized mice along with the use of monoclonal antibodies (mAbs) to tumour necrosis factor-receptor super family 25 (TNFRSF25), expressed on regulatory T (Treg) cells. C57BL/6 mice, which had been sensitized earlier with BALB/c skin allografts, received secondary BALB/c grafts after the primary grafts had been rejected...
April 2017: Immunology
https://www.readbyqxmd.com/read/27757300/mrna-transfected-dendritic-cell-vaccine-in-combination-with-metronomic-cyclophosphamide-as-treatment-for-patients-with-advanced-malignant-melanoma
#13
Troels Holz Borch, Lotte Engell-Noerregaard, Trine Zeeberg Iversen, Eva Ellebaek, Özcan Met, Morten Hansen, Mads Hald Andersen, Per Thor Straten, Inge Marie Svane
INTRODUCTION: Vaccination with dendritic cells (DCs) has generally not fulfilled its promise in cancer immunotherapy due to ineffective translation of immune responses into clinical responses. A proposed reason for this is intrinsic immune regulatory mechanisms, such as regulatory T cells (Tregs). A metronomic regimen of cyclophosphamide (mCy) has been shown to selectively deplete Tregs. To test this in a clinical setting, we conducted a phase I trial to evaluate the feasibility and safety of vaccination with DCs transfected with mRNA in combination with mCy in patients with metastatic malignant melanoma (MM)...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27717798/enterococcus-hirae-and-barnesiella-intestinihominis-facilitate-cyclophosphamide-induced-therapeutic-immunomodulatory-effects
#14
Romain Daillère, Marie Vétizou, Nadine Waldschmitt, Takahiro Yamazaki, Christophe Isnard, Vichnou Poirier-Colame, Connie P M Duong, Caroline Flament, Patricia Lepage, Maria Paula Roberti, Bertrand Routy, Nicolas Jacquelot, Lionel Apetoh, Sonia Becharef, Sylvie Rusakiewicz, Philippe Langella, Harry Sokol, Guido Kroemer, David Enot, Antoine Roux, Alexander Eggermont, Eric Tartour, Ludger Johannes, Paul-Louis Woerther, Elisabeth Chachaty, Jean-Charles Soria, Encouse Golden, Silvia Formenti, Magdalena Plebanski, Mutsa Madondo, Philip Rosenstiel, Didier Raoult, Vincent Cattoir, Ivo Gomperts Boneca, Mathias Chamaillard, Laurence Zitvogel
The efficacy of the anti-cancer immunomodulatory agent cyclophosphamide (CTX) relies on intestinal bacteria. How and which relevant bacterial species are involved in tumor immunosurveillance, and their mechanism of action are unclear. Here, we identified two bacterial species, Enterococcus hirae and Barnesiella intestinihominis that are involved during CTX therapy. Whereas E. hirae translocated from the small intestine to secondary lymphoid organs and increased the intratumoral CD8/Treg ratio, B. intestinihominis accumulated in the colon and promoted the infiltration of IFN-γ-producing γδT cells in cancer lesions...
October 18, 2016: Immunity
https://www.readbyqxmd.com/read/27687804/gemcitabine-reduces-mdscs-tregs-and-tgf%C3%AE-1-while-restoring-the-teff-treg-ratio-in-patients-with-pancreatic-cancer
#15
Emma Eriksson, Jessica Wenthe, Sandra Irenaeus, Angelica Loskog, Gustav Ullenhag
BACKGROUND: Cancer immunotherapy can be potentiated by conditioning regimens such as cyclophosphamide, which reduces the level of regulatory T cells (tregs). However, myeloid suppressive cells are still remaining. Accordingly to previous reports, gemcitabine improves immune status of cancer patients. In this study, the role of gemcitabine was further explored to map its immunological target cells and molecules in patients with pancreatic cancer. METHODS: Patient blood was investigated by flow cytometry and cytokine arrays at different time points during gemcitabine treatment...
September 29, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27680685/ccr2-influences-t-regulatory-cell-migration-to-tumors-and-serves-as-a-biomarker-of-cyclophosphamide-sensitivity
#16
Pierre-Louis Loyher, Juliette Rochefort, Camille Baudesson de Chanville, Pauline Hamon, Géraldine Lescaille, Chloé Bertolus, Maude Guillot-Delost, Matthew F Krummel, François M Lemoine, Christophe Combadière, Alexandre Boissonnas
The CCL2 chemokine receptor CCR2 drives cancer by mediating the recruitment of monocytes and myeloid-derived suppressor cells to the tumor microenvironment. In this study, we extend the significance of CCR2 in this setting by identifying a new role for it in mediating recruitment of CD4(+) T regulatory cells (Treg). Following tumor initiation, an expanded population of CCR2(+) Tregs required CCR2 expression to traffic between draining lymph nodes (dLN) and the tumor. This Treg subset was enriched in the fraction of tumor antigen-specific cells in the dLN, where they displayed an activated immunosuppressive phenotype...
November 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/27646791/the-effect-of-cyclophosphamide-on-the-immune-system-implications-for-clinical-cancer-therapy
#17
REVIEW
Martina Ahlmann, Georg Hempel
Cyclophosphamide is an alkylating agent belonging to the group of oxazaphosporines. As cyclophosphamide is in clinical use for more than 40 years, there is a lot of experience using this drug for the treatment of cancer and as an immunosuppressive agent for the treatment of autoimmune and immune-mediated diseases. Besides antimitotic and antireplicative effects, cyclophosphamide has immunosuppressive as well as immunomodulatory properties. Cyclophosphamide shows selectivity for T cells and is therefore now frequently used in tumour vaccination protocols and to control post-transplant allo-reactivity in haplo-identical unmanipulated bone marrow after transplantation...
October 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27545090/improvement-of-anti-tumor-immunity-of-fibroblast-activation-protein-%C3%AE-based-vaccines-by-combination-with-cyclophosphamide-in-a-murine-model-of-breast-cancer
#18
Qiu Xia, Fang-Fang Zhang, Fei Geng, Chen-Lu Liu, Yu-Qian Wang, Ping Xu, Zhen-Zhen Lu, Yu Xie, Hui Wu, Yan Chen, Yong Zhang, Wei Kong, Xiang-Hui Yu, Hai-Hong Zhang
Fibroblast activation protein α (FAPα) is expressed in cancer-associated fibroblasts (CAFs), which are the main type of cells in the tumor microenvironment. CAFs exert immunosuppressive activity, which can weaken the effects of cancer immunotherapy and mainly account for poor outcomes with therapeutic vaccines. To better target and destroy CAFs, a FAPα vaccine using a modified vaccinia ankara (MVA) vector was constructed and used with a DNA vaccine reported in our previous work for heterologous prime-boost immunizations in mice...
December 2016: Cellular Immunology
https://www.readbyqxmd.com/read/27495172/inhibition-of-mouse-breast-adenocarcinoma-growth-by-ablation-with-intratumoral-alpha-irradiation-combined-with-inhibitors-of-immunosuppression-and-cpg
#19
Hila Confino, Michael Schmidt, Margalit Efrati, Ilan Hochman, Viktor Umansky, Itzhak Kelson, Yona Keisari
It has been demonstrated that aggressive in situ tumor destruction (ablation) could lead to the release of tumor antigens, which can stimulate anti-tumor immune responses. We developed an innovative method of tumor ablation based on intratumoral alpha-irradiation, diffusing alpha-emitters radiation therapy (DaRT), which efficiently ablates local tumors and enhances anti-tumor immunity. In this study, we investigated the anti-tumor potency of a treatment strategy, which combines DaRT tumor ablation with two approaches for the enhancement of anti-tumor reactivity: (1) neutralization of immunosuppressive cells such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) and (2) boost the immune response by the immunoadjuvant CpG...
October 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27341020/definitive-activation-of-endogenous-antitumor-immunity-by-repetitive-cycles-of-cyclophosphamide-with-interspersed-toll-like-receptor-agonists
#20
Soraya Zorro Manrique, Ana L Dominguez, Noweeda Mirza, Christopher D Spencer, Judy M Bradley, James H Finke, James J Lee, Larry R Pease, Sandra J Gendler, Peter A Cohen
Many cancers both evoke and subvert endogenous anti-tumor immunity. However, immunosuppression can be therapeutically reversed in subsets of cancer patients by treatments such as checkpoint inhibitors or Toll-like receptor agonists (TLRa). Moreover, chemotherapy can leukodeplete immunosuppressive host elements, including myeloid-derived suppressor cells (MDSCs) and regulatory T-cells (Tregs). We hypothesized that chemotherapy-induced leukodepletion could be immunopotentiated by co-administering TLRa to emulate a life-threatening infection...
July 12, 2016: Oncotarget
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