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Microenvironment lymphoma

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https://www.readbyqxmd.com/read/28529947/immune-checkpoint-blockade-for-hematologic-malignancies-a-review
#1
REVIEW
Matthew J Pianko, Yuzhou Liu, Srishti Bagchi, Alexander M Lesokhin
Immune checkpoint blockade has revolutionized the treatment of cancer, with impressive responses seen in a broad variety of tumor types. Blockade of immune checkpoints and immune signaling antibodies has shown promise in multiple types of hematologic malignancies (HMs), with dramatic single agent responses for pembrolizumab and nivolumab in Hodgkin lymphoma (HL). In this review, we outline the current state of immune checkpoint blockade drug development in HMs, and discuss mechanisms of activity and resistance, and highlight potential targets in the immune tumor microenvironment (TME)...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28515410/differentiating-between-central-nervous-system-lymphoma-and-high-grade-glioma-using-dynamic-susceptibility-contrast-and-dynamic-contrast-enhanced-mr-imaging-with-histogram-analysis
#2
Kazuhiro Murayama, Yuya Nishiyama, Yuichi Hirose, Masato Abe, Shigeharu Ohyu, Ayako Ninomiya, Takashi Fukuba, Kazuhiro Katada, Hiroshi Toyama
PURPOSE: We evaluated the diagnostic performance of histogram analysis of data from a combination of dynamic susceptibility contrast (DSC)-magnetic resonance imaging (MRI) and dynamic contrast-enhanced (DCE)-MRI for quantitative differentiation between central nervous system lymphoma (CNSL) and high-grade glioma (HGG), with the aim of identifying useful perfusion parameters as objective radiological markers for differentiating between them. METHODS: Eight lesions with CNSLs and 15 with HGGs who underwent MRI examination, including DCE and DSC-MRI, were enrolled in our retrospective study...
May 18, 2017: Magnetic Resonance in Medical Sciences: MRMS
https://www.readbyqxmd.com/read/28512625/using-murine-models-to-investigate-tumor-lymphoid-interactions-spotlight-on-chronic-lymphocytic-leukemia-and-angioimmunoblastic-t-cell-lymphoma
#3
REVIEW
Tyler A Herek, Christine E Cutucache
The role of the tumor microenvironment in leukemias and lymphomas is well established, yet the intricacies of how the malignant cells regulate and influence their non-malignant counterparts remain elusive. For example, chronic lymphocytic leukemia (CLL) is an expansion of malignant CD5(+)CD19(+) B cells, yet the non-malignant T cells play just as large of a role in disease presentation and etiology. Herein, we review the dynamic tumor cell to lymphoid repertoire interactions found in two non-Hodgkin's lymphoma subtypes: CLL and angioimmunoblastic T-cell lymphoma...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28512240/sting-activation-reverses-lymphoma-mediated-resistance-to-antibody-immunotherapy
#4
Lekh N Dahal, Lang Dou, Khiyam Hussain, Rena Liu, Alexander Earley, Kerry L Cox, Salome Murinello, Ian Tracy, Francesco Forconi, Andrew J Steele, Patrick Duriez, Diego Gomez-Nicola, Jessica L Teeling, Martin J Glennie, Mark S Cragg, Stephen A Beers
Tumors routinely attract and co-opt macrophages to promote their growth, angiogenesis and metastasis. Macrophages are also the key effector cell for monoclonal antibody (mAb) therapies. Here we report that the tumor microenvironment creates an immunosuppressive signature on tumor-associated macrophages (TAM) which favors expression of inhibitory rather than activating Fcγ receptors (FcγR), thereby limiting the efficacy of mAb immunotherapy. We assessed a panel of TLR and STING agonists (a) for their ability to reprogram macrophages to a state optimal for mAb immunotherapy...
May 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28508176/the-prognostic-role-of-cd68-and-foxp3-expression-in-patients-with-primary-central-nervous-system-lymphoma
#5
Hyunsoo Cho, Se Hoon Kim, Soo-Jeong Kim, Jong Hee Chang, Woo Ick Yang, Chang-Ok Suh, June-Won Cheong, Yu Ri Kim, Jung Yeon Lee, Ji Eun Jang, Yundeok Kim, Yoo Hong Min, Jin Seok Kim
The prognostic role of CD68 and FoxP3 in primary central nervous system lymphoma (PCNSL) has not been evaluated. Thus, we examined the prognostic significance of CD68 and FoxP3 expression in tumor samples of 76 newly diagnosed immunocompetent PCNSL patients. All patients were treated initially with high-dose methotrexate (HD-MTX)-based chemotherapy, and 16 (21.1%) patients received upfront autologous stem cell transplantation (ASCT) consolidation. High expression of CD68 (>55 cells/high-power field) or FoxP3 (>15 cells/high-power field) was observed in 10 patients, respectively...
May 15, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28507793/composite-biomarkers-defined-by-multiparametric-immunofluorescence-analysis-identify-alk-positive-adenocarcinoma-as-a-potential-target-for-immunotherapy
#6
Hélène Roussel, Eléonore De Guillebon, Lucie Biard, Marion Mandavit, Laure Gibault, Elisabeth Fabre, Martine Antoine, Paul Hofman, Michèle Beau-Faller, Hélène Blons, Claire Danel, Françoise Le Pimpec Barthes, Alain Gey, Clémence Granier, Marie Wislez, Pierre Laurent-Puig, Stéphane Oudard, Patrick Bruneval, Cécile Badoual, Jacques Cadranel, Eric Tartour
Anaplastic lymphoma kinase (ALK) inhibitors have been successfully developed for non-small cell lung carcinoma (NSCLC) displaying chromosomal rearrangements of the ALK gene, but unfortunately resistance invariably occurs. Blockade of the PD-1-PD-L1/2 inhibitory pathway constitutes a breakthrough for the treatment of NSCLC. Some predictive biomarkers of clinical response to this therapy are starting to emerge, such as PD-L1 expression by tumor/stromal cells and infiltration by CD8(+) T cells expressing PD-1...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28504999/tumor-microenvironment-and-checkpoint-molecules-in-primary-cutaneous-diffuse-large-b-cell-lymphoma-new-therapeutic-targets
#7
Christina Mitteldorf, Arbeneshe Berisha, Monique C Pfaltz, Sigrid M C Broekaert, Michael P Schön, Katrin Kerl, Werner Kempf
Programmed death ligand 1 (PD-L1) is expressed by 20% to 57% of systemic diffuse large B cell lymphomas (DLBCLs). PD-L1 expression in primary cutaneous DLBCL (pcDLBCL) has not been studied so far. Sixteen paraffin-embedded tissue samples of pcDLBCL (13 leg type [LT], 3 others [OT]) were investigated for PD-1, PD-L1, and CD33 expression and the cellular composition of the tumor microenvironment, focusing on myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages. Membrane-bound PD-L1 expression by the tumor cells was observed in all samples, albeit to a variable extent (19...
May 12, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28480764/novel-agents-in-mantle-cell-lymphoma
#8
David Tucker, Simon Rule
Mantle cell lymphoma (MCL) usually takes an aggressive clinical course and carries a poor prognosis. Recently, progress has been made in the treatment of MCL including the development of a number of novel agents which target intracellular pathways and the extracellular microenvironment. These agents have transformed the landscape of available therapeutic options. Areas covered: The current literature on the novel agents which currently hold a licence for the treatment of MCL in the context of front-line therapy and in the relapsed/refractory setting is summarized...
May 17, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28446910/are-mast-cells-masters-in-cancer
#9
REVIEW
Gilda Varricchi, Maria Rosaria Galdiero, Stefania Loffredo, Giancarlo Marone, Raffaella Iannone, Gianni Marone, Francescopaolo Granata
Prolonged low-grade inflammation or smoldering inflammation is a hallmark of cancer. Mast cells form a heterogeneous population of immune cells with differences in their ultra-structure, morphology, mediator content, and surface receptors. Mast cells are widely distributed throughout all tissues and are stromal components of the inflammatory microenvironment that modulates tumor initiation and development. Although canonically associated with allergic disorders, mast cells are a major source of pro-tumorigenic (e...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28438619/implications-of-infiltrating-immune-cells-within-bone-marrow-of-patients-with-diffuse-large-b-cell-lymphoma
#10
Juhyeon Jeong, Eun Ji Oh, Woo Ick Yang, Soo Jeong Kim, Sun Och Yoon
The implications of infiltrating immune cells, especially T cells and macrophages, in the bone marrow (BM) microenvironment of patients with diffuse large B-cell lymphoma (DLBCL) have rarely been studied. We aimed to investigate the significance of infiltrating immune cells in the BM microenvironment as a prognostic factor for DLBCL patients. Using the initial pretreatment BM biopsy obtained from 198 DLBCL patients, we semiquantitatively evaluated CD3+ T cells, CD8+ T cells, and CD163+ macrophages that infiltrate into the paratrabecular and interstitial areas of BM by immunohistochemistry and analyzed their clinicopathological and prognostic implications...
April 21, 2017: Human Pathology
https://www.readbyqxmd.com/read/28435287/serum-galectin-1-in-patients-with-multiple-myeloma-associations-with-survival-angiogenesis-and-biomarkers-of-macrophage-activation
#11
Morten Nørgaard Andersen, Maja Ludvigsen, Niels Abildgaard, Irma Petruskevicius, Rikke Hjortebjerg, Mette Bjerre, Bent Honoré, Holger J Møller, Niels F Andersen
Galectin-1 (Gal-1) is known to regulate cell signaling within the immune system and may be a target for new anticancer immune therapy. In patients with chronic lymphocytic leukemia (CLL) and classical Hodgkin lymphoma (cHL), high levels of Gal-1 within the tumor microenvironment were associated with worse disease state or poor outcome. Gal-1 can be secreted from cells by an unknown mechanism, and levels in blood samples were associated with high tumor burden and worse disease state in cHL and CLL patients. However, serum levels of Gal-1 have never been investigated in patients with multiple myeloma (MM)...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28426555/creating-artificial-lymphoid-tissues-to-study-immunity-and-hematological-malignancies
#12
Shivem B Shah, Ankur Singh
PURPOSE OF REVIEW: The specialized microenvironments of lymphoid tissue affect immune cell function and progression of disease. However, current animal models are low throughput and a large number of human diseases are difficult to model in animals. Animal models are less amenable to manipulation of tissue niche components, signalling pathways, epigenetics, and genome editing than ex vivo models. On the other hand, conventional 2D cultures lack the physiological relevance to study precise microenvironmental interactions...
April 19, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28424405/the-bruton-s-tyrosine-kinase-inhibitor-ibrutinib-exerts-immunomodulatory-effects-through-regulation-of-tumor-infiltrating-macrophages
#13
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/28424162/pembrolizumab-in-patients-with-chronic-lymphocytic-leukemia-with-richter-s-transformation-and-relapsed-cll
#14
Wei Ding, Betsy R LaPlant, Timothy G Call, Sameer A Parikh, Jose F Leis, Rong He, Tait D Shanafelt, Sutapa Sinha, Jennifer Le-Rademacher, Andrew L Feldman, Thomas M Habermann, Thomas E Witzig, Gregory A Wiseman, Yi Lin, Erik Asmus, Grzegorz S Nowakowski, Michael J Conte, Deborah A Bowen, Casey N Aitken, Daniel L Van Dyke, Patricia T Greipp, Xin Liu, Xiaosheng Wu, Henan Zhang, Charla R Secreto, Shulan Tian, Esteban Braggio, Linda E Wellik, Ivana Micallef, David S Viswanatha, Huihuang Yan, Asher A Chanan-Khan, Neil E Kay, Haidong Dong, Stephen M Ansell
CLL patients progressed early on ibrutinib often develop Richter's transformation (RT) with short survival about 4 months. Preclinical studies suggest that programmed death 1 (PD-1) pathway is critical to inhibit immune surveillance in CLL. This phase 2 study MC1485 (NCT02332980) was designed to test the efficacy and safety of pembrolizumab, a humanized PD-1-blocking antibody, at a dose of 200 mg every 3 weeks in relapsed and transformed CLL. Twenty-five patients including 16 relapsed CLL and 9 RT (all proven diffuse large cell lymphoma) patients were enrolled and 60% received prior ibrutinib...
April 19, 2017: Blood
https://www.readbyqxmd.com/read/28423548/axl-acts-as-a-tumor-suppressor-by-regulating-light-expression-in-t-lymphoma
#15
Eun-Hee Lee, Eun-Mi Kim, Kon-Young Ji, A-Reum Park, Ha-Rim Choi, Hwa-Youn Lee, Su-Man Kim, Byung Yeoup Chung, Chul-Hong Park, Hyo Jin Choi, Young-Hyeh Ko, Hyoung-Woo Bai, Hyung-Sik Kang
Axl is an oncogenic receptor tyrosine kinase that plays a role in many cancers. LIGHT (Lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells) is a ligand that induces robust anti-tumor immunity by enhancing the recruitment and activation of effector immune cells at tumor sites. We observed that mouse EL4 and human Jurkat T lymphoma cells that stably overexpressed Axl also showed high expression of LIGHT. When Jurkat-Axl cells were treated with Gas6, a ligand for Axl, LIGHT expression was upregulated through activation of the PI3K/AKT signaling pathway and transcriptional induction by Sp1...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423378/innovative-treatment-concepts-for-cutaneous-t-cell-lymphoma-based-on-microenvironment-modulation
#16
Katharina Leuchte, Max Schlaak, Rudolf Stadler, Sebastian Theurich, Michael von Bergwelt-Baildon
Cutaneous T-cell lymphomas (CTCL) are a rare and biologically heterogeneous malignant entity comprising mycosis fungoides and Sézary syndrome as the most common subtypes. The current treatment outcome is characterized by high rates of relapse, but survival is usually not significantly shortened in low-stage disease. This is different in tumor-stage disease or aggressive CTCL subtypes where survival is significantly reduced. Recent advances have been made on several levels of tumor biology: Whole genome sequencing has resulted in novel strategies of NF-κB or JAK inhibition, ongoing translational research has revealed new targets like CD30 or CCR4, and, finally, research focusing on impaired immunosurveillance has gained more importance...
2017: Oncology Research and Treatment
https://www.readbyqxmd.com/read/28419513/genetic-recombination-between-stromal-and-cancer-cells-results-in-highly-malignant-cells-identified-by-color-coded-imaging-in-a-mouse-lymphoma-model
#17
Miki Nakamura, Atsushi Suetsugu, Kousuke Hasegawa, Takuro Matsumoto, Hitomi Aoki, Takahiro Kunisada, Masahito Shimizu, Shigetoyo Saji, Hisataka Moriwaki, Robert M Hoffman
The tumor microenvironment (TME) promotes tumor growth and metastasis. We previously established the color-coded EL4 lymphoma model with red fluorescent protein expressing EL4 implanted in transgenic C57BL/6 green fluorescent protein (GFP) mice. Color-coded imaging of the lymphoma tumor suggested an important role of stromal cells in lymphoma progression and metastasis. In the present study, we used color-coded imaging of RFP-lymphoma cells and GFP stromal cells to identify yellow-fluorescent recombinant cells appearing only during metastasis...
April 17, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28416797/unification-of-de-novo-and-acquired-ibrutinib-resistance-in-mantle-cell-lymphoma
#18
Xiaohong Zhao, Tint Lwin, Ariosto Silva, Bijal Shah, Jiangchuan Tao, Bin Fang, Liang Zhang, Kai Fu, Chengfeng Bi, Jiannong Li, Huijuan Jiang, Mark B Meads, Timothy Jacobson, Maria Silva, Allison Distler, Lancia Darville, Ling Zhang, Ying Han, Dmitri Rebatchouk, Maurizio Di Liberto, Lynn C Moscinski, John M Koomen, William S Dalton, Kenneth H Shain, Michael Wang, Eduardo Sotomayor, Jianguo Tao
The novel Bruton's tyrosine kinase inhibitor ibrutinib has demonstrated high response rates in B-cell lymphomas; however, a growing number of ibrutinib-treated patients relapse with resistance and fulminant progression. Using chemical proteomics and an organotypic cell-based drug screening assay, we determine the functional role of the tumour microenvironment (TME) in ibrutinib activity and acquired ibrutinib resistance. We demonstrate that MCL cells develop ibrutinib resistance through evolutionary processes driven by dynamic feedback between MCL cells and TME, leading to kinome adaptive reprogramming, bypassing the effect of ibrutinib and reciprocal activation of PI3K-AKT-mTOR and integrin-β1 signalling...
April 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28411252/prognostic-relevance-of-cd163-and-cd8-combined-with-ezh2-and-gain-of-chromosome-18-in-follicular-lymphoma-a-study-by-the-lunenburg-lymphoma-biomarker-consortium
#19
Wendy B C Stevens, Matias Mendeville, Robert Redd, Andrew J Clear, Reno Bladergroen, Maria Calaminici, Andreas Rosenwald, Eva Hoster, Wolfgang Hiddemann, Philippe Gaulard, Luc Xerri, Gilles Salles, Wolfram Klapper, Michael Phreundschuh, Andrew Jack, Randy D Gascoyne, Yasodha Natkunam, Ranjana Advani, Eva Kimby, Birgitta Sander, Laurie Sehn, Anton Hagenbeek, John Raemaekers, John Gribben, Marie Jose' Kersten, Bauke Ylstra, Edie Weller, Daphne de Jong
In follicular lymphoma, studies addressing the prognostic value of microenvironment-related immunohistochemical markers and tumor cell-related genetic markers have yielded conflicting results, precluding implementation in practice. Therefore, the Lunenburg Lymphoma Biomarker Consortium performed a validation study evaluating published markers. To maximize sensitivity, an end-of-spectrum design was applied for 122 uniformly immunochemotherapy-treated follicular lymphoma patients retrieved from international trials and registries; early failure: progression or lymphoma-related death <2 years versus long remission: response duration of >5 years...
April 14, 2017: Haematologica
https://www.readbyqxmd.com/read/28408460/can-histologic-transformation-of-follicular-lymphoma-be-predicted-and-prevented
#20
Robert Kridel, Laurie H Sehn, Randy D Gascoyne
Transformation to aggressive lymphoma is a critical event in the clinical course of follicular lymphoma patients. Yet, it is a challenge to reliably predict transformation at the time of diagnosis. Understanding the risk of transformation would be useful to guide and monitor patients, as well as for evaluation of novel treatment strategies that could potentially prevent transformation. Herein, we review the contribution of clinical, pathological and genetic risk factors to transformation. Patients with multiple clinical high-risk factors are at elevated risk of transformation but we are currently lacking a prognostic index that would specifically address transformation rather than disease progression or overall survival...
April 13, 2017: Blood
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