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Treg cyclophosphamide

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
Shuyu E, Aman Seth, Peter Vogel, Matt Sommers, Taren Ong, Asha B Pillai
Non-myeloablative conditioning using total lymphoid irradiation (TLI) and rabbit anti-thymocyte serum (ATS) (the murine pre-clinical equivalent of anti-thymocyte globulin/ATG) facilitates immune tolerance after bone marrow transplantation (BMT) across major histocompatibility complex (MHC) disparities and may be a useful strategy for non-malignant disorders. We previously reported that donor effector T cell function and GVHD are regulated via recipient invariant natural killer T cell (iNKT cell) IL-4-driven expansion of donor Foxp3(+) naturally occurring Treg...
March 28, 2017: Blood
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...
January 25, 2017: Cytotherapy
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
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
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
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
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
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...
September 28, 2016: Cancer Research
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
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...
August 16, 2016: Cellular Immunology
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
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
Juan C Gomez-Gelvez, Mohamed E Salama, Sherrie L Perkins, Matthew Leavitt, Kedar V Inamdar
OBJECTIVES: We evaluated the prognostic impact of cell-of-origin classification as well as intratumoral regulatory T cells (Tregs), macrophages, and microvessel density (MVD) on 115 patients (74 in the training set and 41 in the validation set) diagnosed with de novo diffuse large B-cell lymphoma (DLBCL) and uniformly treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. METHODS: The prognostic impact of Tregs, macrophages, and MVD was evaluated using FOXP3, CD68, and CD34 immunohistochemical stains, respectively...
April 2016: American Journal of Clinical Pathology
Jessica Stokes, Emely A Hoffman, Yi Zeng, Nicolas Larmonier, Emmanuel Katsanis
Advances in haploidentical bone marrow transplantation (h-BMT) have drastically broadened the treatment options for patients requiring BMT. The possibility of significantly reducing the complications resulting from graft-versus-host disease (GvHD) with the administration of post-transplant cyclophosphamide (PT-CY) has substantially improved the efficacy and applicability of T cell-replete h-BMT. However, higher frequency of disease recurrence remains a major challenge in h-BMT with PT-CY. There is a critical need to identify novel strategies to prevent GvHD while sparing the graft-versus-leukaemia (GvL) effect in h-BMT...
July 2016: British Journal of Haematology
S Denies, L Cicchelero, H de Rooster, S Daminet, I Polis, I Van de Maele, N N Sanders
Metronomic chemotherapy stimulates the immune response via depletion of regulatory T cells (Tregs) and suppresses angiogenesis by modulating the secretion of thrombospondin-1 (TSP-1) and vascular endothelial growth factor (VEGF). In this study, blood was collected from 10 healthy dogs and from 30 canine cancer patients before and 2 and 4 weeks after treatment with metronomic temozolomide (6.6 mg m(-2) ), cyclophosphamide (12.5 mg m(-2) ) or cyclophosphamide and temozolomide. The percentage of circulating CD25(+) Foxp3(+) CD4(+) Tregs and the plasma levels of TSP-1 and VEGF were measured...
June 2017: Veterinary and Comparative Oncology
Xiao-Dan Han, Jian Zhou, Feng-Kuan Yu, Bai-Jun Fang, Yan-Li Zhang, Xu-Dong Wei, Yong-Ping Song
OBJECTIVE: To evaluate the efficiency and safety of rituximab and dexamethasone combined with cyclophosphamide for treating patients with relapsed and refractory immune thrombocytopenia (ITP). METHODS: Twelve patients with relapsed and refractory immune thrombocytopenia were prospectively enrolled in this study, and received rituximab 375 mg/m(2) once a week for 4 weeks, dexamethasone 40 mg once a day for consecutive 4 days, and cyclophosphamide 500 mg/m(2) biweekly for 2 weeks...
February 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
Junhua Xie, Shaoping Nie, Qiang Yu, Junyi Yin, Tao Xiong, Deming Gong, Mingyong Xie
The balance of T helper cells 17 (Th17)/regulatory T cells (Treg) plays a key role in maintaining a normal immune response. It is well-known that cyclophosphamide (CTX) applied at high dose often damages the immune system by inhibiting immune cell proliferation. In this study, the immunomodulating effects of Lactobacillus plantarum NCU116 in CTX-induced immunosuppression mice were investigated. Results showed that the levels of cytokines interleukin (IL)-17 and IL-21 were significantly increased after 10 days of treatment with a high dose of NCU116 (46...
February 17, 2016: Journal of Agricultural and Food Chemistry
Mladen Korbelik, Judit Banáth, Kyi Min Saw
Photodynamic therapy (PDT)-generated cancer vaccine represents an attractive potential application of PDT, therapeutic modality destroying targeted lesions by localized photooxidative stress. Since immunoregulatory cell activity has become recognized as a major obstacle to effective cancer immunotherapy, the present study examined their participation in the therapeutic effect of PDT cancer vaccine. Following protocols from previous studies, mouse with squamous cell carcinoma SCCVII tumors were vaccinated by SCCVII cells treated by PDT and response monitored by tumor size measurement...
2015: International Journal of Molecular Sciences
R M Rasmussen, I D Kurzman, B J Biller, A Guth, D M Vail
Maximally tolerated dose (MTD) and metronomic dose chemotherapeutic approaches alter the immune system and the angiogenic process in different yet potentially complementary ways. A combination of MTD doxorubicin (MTD-DOX) and metronomic cyclophosphamide (mCTX) protocol was evaluated for safety and effect on circulating regulatory T (Treg) cells. We found that mCTX can be safely administered with MTD-DOX in tumour-bearing dogs. Both combination DOX/mCTX and single-agent DOX resulted in significant depletions of circulating lymphocytes throughout the chemotherapy cycle without apparent selectivity for Tregs...
June 2017: Veterinary and Comparative Oncology
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