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toll like receptors and lymphoma

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https://www.readbyqxmd.com/read/28424405/the-bruton-s-tyrosine-kinase-inhibitor-ibrutinib-exerts-immunomodulatory-effects-through-regulation-of-tumor-infiltrating-macrophages
#1
Lingyan Ping, Ning Ding, Yunfei Shi, Lixia Feng, Jiao Li, Yalu Liu, Yufu Lin, Cunzhen Shi, Xing Wang, Zhengying Pan, Yuqin Song, Jun Zhu
The Bruton's tyrosine kinase (Btk) inhibitor ibrutinib has demonstrated promising efficacy in a variety of hematologic malignancies. However, the precise mechanism of action of the drug remains to be fully elucidated. Tumor-infiltrating macrophages presented in the tumor microenvironment have been shown to promote development and progression of B-cell lymphomas through crosstalk mediated by secreted cytokines and chemokines. Because Btk has been implicated in Toll-like receptor (TLR) signaling pathways that regulate macrophage activation and production of proinflammatory cytokines, we investigated the immunomodulatory effects of Btk inhibitor on macrophages...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28405493/hla-class-i-restricted-myd88-l265p-derived-peptides-as-specific-targets-for-lymphoma-immunotherapy
#2
Annika Nelde, Juliane Sarah Walz, Daniel Johannes Kowalewski, Heiko Schuster, Olaf-Oliver Wolz, Janet Kerstin Peper, Yamel Cardona Gloria, Anton W Langerak, Alice F Muggen, Rainer Claus, Irina Bonzheim, Falko Fend, Helmut Rainer Salih, Lothar Kanz, Hans-Georg Rammensee, Stefan Stevanović, Alexander N R Weber
Genome sequencing has uncovered an array of recurring somatic mutations in different non-Hodgkin lymphoma (NHL) subtypes. If affecting protein-coding regions, such mutations may yield mutation-derived peptides that may be presented by HLA class I proteins and recognized by cytotoxic T cells. A recurring somatic and oncogenic driver mutation of the Toll-like receptor adaptor protein MYD88, Leu265Pro (L265P) was identified in up to 90% of different NHL subtype patients. We therefore screened the potential of MYD88(L265P)-derived peptides to elicit cytotoxic T cell responses as tumor-specific neoantigens...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344752/involvement-of-cbl-b-mediated-macrophage-inactivation-in-insulin-resistance
#3
REVIEW
Tomoki Abe, Katsuya Hirasaka, Takeshi Nikawa
Aging and overnutrition cause obesity in rodents and humans. It is well-known that obesity causes various diseases by producing insulin resistance (IR). Macrophages infiltrate the adipose tissue (AT) of obese individuals and cause chronic low-level inflammation associated with IR. Macrophage infiltration is regulated by the chemokines that are released from hypertrophied adipocytes and the immune cells in AT. Saturated fatty acids are recognized by toll-like receptor 4 (TLR4) and induce inflammatory responses in AT macrophages (ATMs)...
March 15, 2017: World Journal of Diabetes
https://www.readbyqxmd.com/read/28288716/molecular-pathogenesis-of-splenic-and-nodal-marginal-zone-lymphoma
#4
REVIEW
Valeria Spina, Davide Rossi
Genomic studies have improved our understanding of the biological basis of splenic (SMZL) and nodal (NMZL) marginal zone lymphoma by providing a comprehensive and unbiased view of the genes/pathways that are deregulated in these diseases. Consistent with the physiological involvement of NOTCH, NF-κB, B-cell receptor and toll-like receptor signaling in mature B-cells differentiation into the marginal zone B-cells, many oncogenic mutations of genes involved in these pathways have been identified in SMZL and NMZL...
March 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/28241765/heterogeneity-of-toll-like-receptor-9-signaling-in-b-cell-malignancies-and-its-potential-therapeutic-application
#5
REVIEW
Ling Bai, Wei Chen, Jingtao Chen, Wei Li, Lei Zhou, Chao Niu, Wei Han, Jiuwei Cui
Toll-like receptor 9 (TLR9) is expressed in a variety of B-cell malignancies and works as a bridge between innate and adaptive immunity. CpG oligodeoxynucleotides (CpG ODNs), TLR9 agonists, are able to induce anticancer immune responses and exert direct effects against cancer cells, serving as cancer therapeutic agents. Therefore, TLR9 might be a potential therapeutic target for drug development. However, several new evidences have revealed that direct effects of TLR9 agonists on B-cell malignancies is controversial...
February 27, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28214929/myeloid-cells-as-a-target-for-oligonucleotide-therapeutics-turning-obstacles-into-opportunities
#6
REVIEW
Marcin Kortylewski, Dayson Moreira
Immunotherapies emerged as an alternative for cancer treatment, yet their clinical efficacies are still limited, especially in case of solid tumors. Myeloid immune cells, such as macrophages and myeloid-derived suppressor cells (MDSCs), are often hijacked by tumors and become pivotal inhibitors of antitumor immunity. Immunosuppressive functions of tumor-associated myeloid cells result from the activity of Signal Transducer and Activator of Transcription 3 (STAT3), a transcription factor with well-defined tumorigenic and tolerogenic roles in human cancers...
February 18, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28153771/b-cell-function-gene-mutations-in-diffuse-large-b-cell-lymphoma-a-retrospective-cohort-study
#7
Peng-Peng Xu, Hui-Juan Zhong, Yao-Hui Huang, Xiao-Dong Gao, Xia Zhao, Yang Shen, Shu Cheng, Jin-Yan Huang, Sai-Juan Chen, Li Wang, Wei-Li Zhao
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous subtype of non-Hodgkin lymphoma. In addition to clinical and immunophenotypic characteristics, recurrent gene mutations have recently been identified in patients with DLBCL using next-generation sequencing technologies. The aim of this study is to investigate the clinical relevance of B-cell function gene mutations in DLBCL. Clinical analysis was performed on 680 Chinese DLBCL patients (146 non-CR and 534 CR cases) treated with six cycles of 21-day R-CHOP (Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), alone or followed by two additional doses of rituximab consolidation on patients' own intention...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/28147336/dual-inhibition-of-histone-deacetylases-and-phosphoinositide-3-kinase-enhances-therapeutic-activity-against-b-cell-lymphoma
#8
Patrizia Mondello, Enrico Derenzini, Zahra Asgari, John Philip, Elliott J Brea, Venkatraman Seshan, Ronald C Hendrickson, Elisa de Stanchina, David A Scheinberg, Anas Younes
Phosphoinositide 3-kinase (PI3K) and Myc are known to cooperate in promoting the survival and growth of a variety of B-cell lymphomas. While currently there are no small molecule inhibitors of Myc protein, histone deacetylase (HDAC) inhibitors have been shown to reduce levels of Myc protein by suppressing its transcription. We assessed the efficacy of CUDC-907, a new rationally designed dual inhibitor of PI3K and HDACs, in a panel of lymphoma cell lines. CUDC-907 treatment resulted in a dose- and time-dependent growth inhibition and cell death of DLBCL cell lines, irrespective of the cell of origin...
February 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28138030/the-tlr3-agonist-inhibit-drug-efflux-and-sequentially-consolidates-low-dose-cisplatin-based-chemoimmunotherapy-while-reducing-side-effects
#9
Liang Ding, Jing Ren, Dongya Zhang, Yi Li, XiaoFeng Huang, Jianjian Ji, Qingang Hu, Hui Wang, Yanhong Ni, Yayi Hou
The traditional maximum dose density chemotherapy renders the tumor patients not only the tumor remission but the chemotherapy resistance and more adverse side effects. According to the widely positive expression of Toll-like receptor (TLR)-3 in oral squamous cell carcinoma (OSCC) patients (n=166), we here provided an alternative strategy involved the orderly treatment of TLR3 agonist polyinosine-polycytidylic acid (PIC) and low-dose cisplatin. The optimal dose of cisplatin, the novel role of PIC and the side effects of the combined chemotherapy were determined in vitro and in distinct human tumor models in vivo...
January 30, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28101570/inhibition-of-tlr4-protects-rat-islets-against-lipopolysaccharide-induced-dysfunction
#10
Xiao Wang, Qin Min Ge, Fan Bian, Yan Dong, Chun Mei Huang
Oxidative stress leads to dysfunction in pancreatic cells, causing a reduction in insulin secretion following exposure to glucose. Toll-like receptor 4 (TLR4) may be activated by exposure to lipopolysaccharide (LPS) stress. TLR4 may mediate the initiation of inflammatory and immune defense responses; however, the importance of the LPS/TLR4 interaction in apoptosis induced by oxidative stress in pancreatic β cells remains to be elucidated. The present study aimed to investigate the importance of TLR4 during LPS‑induced oxidative stress, apoptosis and dysfunction of insulin secretion in isolated islets of rats...
February 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28099084/mechanisms-and-new-strategies-for-primary-sj%C3%A3-gren-s-syndrome
#11
Clio P Mavragani
Primary Sjögren's syndrome (SS) is a common chronic autoimmune disease characterized by lymphocytic infiltration of exocrine glands, mainly salivary and lacrimal, resulting in oral and ocular dryness, although virtually any organ system can be affected. SS-related systemic manifestations are classified as either related to the presence of periepithelial infiltrates in exocrine and parenchymal organs or resulting from immunocomplex deposition due to B cell hyperactivity with increased risk for B cell lymphoma development...
January 14, 2017: Annual Review of Medicine
https://www.readbyqxmd.com/read/28054376/toll-like-receptor-tlr-7-expression-in-mycosis-fungoides-and-psoriasis-a-case-control-study
#12
A M El Tawdy, I M Amin, R M Abdel Hay, A S Hassan, Z S Gad, L A Rashed
BACKGROUND: Toll-like receptors (TLRs) have been implicated in various dermatological diseases. TLR agonists have the capacity to potently activate the innate immune cells of patients with advanced, refractory, cutaneous T-cell lymphoma (CTCL). AIM: To detect TLR7 gene expression in mycosis fungoides (MF) (a neoplastic skin condition) and to compare it with psoriasis (an inflammatory skin condition) in an attempt to clarify the pathogenic role played by TLR7 in both conditions...
March 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/27980783/plasmodium-chabaudi-infection-induces-aid-expression-in-transitional-and-marginal-zone-b-cells
#13
Joel R Wilmore, Alexander C Maue, Rosemary Rochford
INTRODUCTION: Endemic Burkitt's lymphoma (eBL) is associated with Epstein-Barr virus and repeated malaria infections. A defining feature of eBL is the translocation of the c-myc oncogene to the control of the immunoglobulin promoter. Activation-induced cytidine deaminase (AID) has been shown to be critical for this translocation. Malaria infection induces AID in germinal center B cells, but whether malaria infection more broadly affects AID activation in extrafollicular B cells is unknown...
December 2016: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/27757307/cd1b-autoreactive-t-cells-recognize-phospholipid-antigens-and-contribute-to-antitumor-immunity-against-a-cd1b-t-cell-lymphoma
#14
Sreya Bagchi, Sha Li, Chyung-Ru Wang
Adoptive immunotherapy for cancer treatment is an emerging field of study. Till now, several tumor-derived, peptide-specific T cell responses have been harnessed for treating cancers. However, the contribution of lipid-specific T cells in tumor immunity has been understudied. CD1 molecules, which present self- and foreign lipid antigens to T cells, are divided into group 1 (CD1a, CD1b, and CD1c) and group 2 (CD1d). Although the role of CD1d-restricted natural killer T cells (NKT) in several tumor models has been well established, the contribution of group 1 CD1-restricted T cells in tumor immunity remains obscure due to the lack of group 1 CD1 expression in mice...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27668411/synergy-of-interleukin-10-and-toll-like-receptor-9-signalling-in-b-cell-proliferation-implications-for-lymphoma-pathogenesis
#15
Maren Feist, Judith Kemper, Franziska Taruttis, Thorsten Rehberg, Julia C Engelmann, Wolfram Gronwald, Michael Hummel, Rainer Spang, Dieter Kube
A network of autocrine and paracrine signals defines B cell homeostasis and is thought to be involved in transformation processes. Investigating interactions of these microenvironmental factors and their relation to proto-oncogenes as c-Myc (MYC) is fundamental to understand the biology of B cell lymphoma. Therefore, B cells with conditional MYC expression were stimulated with CD40L, insulin-like growth factor 1, α-IgM, Interleukin-10 (IL10) and CpG alone or in combination. The impact of forty different interventions on cell proliferation was investigated in MYC deprived cells and calculated by linear regression...
March 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27622045/a-novel-tlr7-agonist-reverses-nk-cell-anergy-and-cures-rma-s-lymphoma-bearing-mice
#16
Gabriela Maria Wiedemann, Severin Johannes Jacobi, Michael Chaloupka, Angelina Krächan, Svetlana Hamm, Stefan Strobl, Roland Baumgartner, Simon Rothenfusser, Peter Duewell, Stefan Endres, Sebastian Kobold
Toll-like receptor 7 (TLR7) agonists are potent immune stimulants able to overcome cancer-associated immune suppression. Due to dose-limiting systemic toxicities, only the topically applied TLR7 agonist (imiquimod) has been approved for therapy of skin tumors. There is a need for TLR7-activating compounds with equivalent efficacy but less toxicity. SC1, a novel small molecule agonist for TLR7, is a potent type-1 interferon inducer, comparable to the reference TLR7 agonist resiquimod, yet with lower induction of proinflammatory cytokines...
July 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27602749/toll-like-receptors-targeting-technology-for-the-treatment-of-lymphoma
#17
Maria Batool, Muhammad Ayaz Anwar, Sangdun Choi
The crucial role of Toll-like Receptors (TLRs) in innate and adaptive immune systems is well discussed in the literature. In cancer, TLRs act as a double-edged sword that can promote or suppress tumor growth. Areas covered: In this article, the authors uncover the potential role of TLRs in lymphomas, which are cancers related to the lymphatic system and blood cells. TLRs are de facto inflammation-inducing receptors that can either worsen disease or ameliorate lymphoma treatment. From this perspective, the usage of TLRs to modulate the immune system toward lymphoma regression is desirable...
November 2016: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/27503954/conformational-dynamics-of-cancer-associated-myd88-tir-domain-mutant-l252p-l265p-allosterically-tilts-the-landscape-toward-homo-dimerization
#18
Chendi Zhan, Ruxi Qi, Guanghong Wei, Emine Guven-Maiorov, Ruth Nussinov, Buyong Ma
MyD88 is an essential adaptor protein, which mediates the signaling of the toll-like and interleukin-1 receptors' superfamily. The MyD88 L252P (L265P) mutation has been identified in diffuse large B-cell lymphoma. The identification of this mutation has been a major advance in the diagnosis of patients with aldenstrom macroglobulinemia and related lymphoid neoplasms. Here we used computational methods to characterize the conformational effects of the mutation. Our molecular dynamics simulations revealed that the mutation allosterically quenched the global conformational dynamics of the toll/IL-1R (TIR) domain, and readjusted its salt bridges and dynamic community network...
September 2016: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/27503123/c-cbl-mediated-ubiquitination-of-irf3-negatively-regulates-ifn-%C3%AE-production-and-cellular-antiviral-response
#19
Xibao Zhao, Huihui Zhu, Juan Yu, Hongrui Li, Jiafeng Ge, Weilin Chen
Induction of type I interferon is a fundamental cellular response to viral infection. Interferon regulatory factor 3 (IRF3) plays an essential role in Toll-like receptor (TLR) and retinoic acid-inducible gene I (RIG-I) mediated induction of type I interferon and host antiviral responses. However, posttranslational regulation of IRF3 remains to be fully understood. In this study, we identified E3 ubiquitin ligase Casitas B-lineage lymphoma (c-Cbl) as a negative regulator for IRF3 protein stability and IFN-β signal pathway...
November 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27491692/nf-%C3%AE%C2%BAb-activation-in-chronic-lymphocytic-leukemia-a-point-of-convergence-of-external-triggers-and-intrinsic-lesions
#20
Larry Mansouri, Nikos Papakonstantinou, Stavroula Ntoufa, Kostas Stamatopoulos, Richard Rosenquist
The nuclear factor-κB (NF-κB) pathway is constitutively activated in chronic lymphocytic leukemia (CLL) patients, and hence plays a major role in disease development and evolution. In contrast to many other mature B-cell lymphomas, only a few recurrently mutated genes involved in canonical or non-canonical NF-κB activation have been identified in CLL (i.e. BIRC3, MYD88 and NFKBIE mutations) and often at a low frequency. On the other hand, CLL B cells seem 'addicted' to the tumor microenvironment for their survival and proliferation, which is primarily mediated by interaction through a number of cell surface receptors, e...
August 2016: Seminars in Cancer Biology
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