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Microenvironment lymphoma

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https://www.readbyqxmd.com/read/28822058/immune-dysfunction-in-non-hodgkin-lymphoma-avenues-for-new-immunotherapy-based-strategies
#1
REVIEW
Lorenzo Falchi
PURPOSE OF THIS REVIEW: The present review focuses on key aspects of non-Hodgkin lymphoma (NHL) evasion of immune surveillance and how these can be leveraged to devise effective immunotherapy strategies. RECENT FINDINGS: In recent years, significant progress has been made in the field of cancer immunotherapy. In particular, the remarkable clinical results of anti-programmed death (PD)-1/PD-ligand (L)1 antibodies are revolutionizing the treatment approach to multiple solid and hematologic tumors...
August 18, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28819821/anti-pd-1-antibodies-as-a-therapeutic-strategy-in-classical-hodgkin-lymphoma
#2
REVIEW
Michael D Jain, John Kuruvilla
Classical Hodgkin lymphoma (cHL) is defined by malignant Reed-Sternberg (RS) cells that recruit non-malignant immune cells into a supportive tumour microenvironment. In cHL, this is driven, in part, by genomic alterations of the 9p24.1 locus encoding the immune checkpoint ligands PD-L1 and PD-L2. Therapeutic anti-PD-1 antibodies have been developed that competitively inhibit the interaction between PD-1 and its ligands. Clinical trials of anti-PD-1 antibodies in cHL demonstrate high overall response rates but relapses still occur and new clinical challenges exist for toxicity management and response assessment...
August 17, 2017: Drugs
https://www.readbyqxmd.com/read/28815730/loss-of-bmi-1-dampens-migration-and-emt-of-colorectal-cancer-in-inflammatory-microenvironment-through-tlr4-md-2-myd88-mediated-nf-%C3%AE%C2%BAb-signaling
#3
Kai Ye, Qi-Wei Chen, Ya-Feng Sun, Jian-An Lin, Jian-Hua Xu
Increasing evidence from various clinical and experimental studies has demonstrated that the inflammatory microenvironment created by immune cells facilitates tumor migration. Epithelial-mesenchymal transition (EMT) is involved in the progression of cancer invasion and metastasis in an inflammatory microenvironment. B-lymphoma Moloney murine leukemia virus insertion region 1 (BMI-1) acts as an oncogene in various tumors. Ectopic expression of Bmi-1 have an effect on EMT and invasiveness. The purpose of this study was to investigate the efficacy of BMI-1 on inflammation-induced tumor migration and EMT and the underlying mechanism...
August 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28811825/ethanol-extract-of-mylabris-phalerata-inhibits-m2-polarization-induced-by-recombinant-il-4-and-il-13-in-murine-macrophages
#4
Hwan-Suck Chung, Bong-Seon Lee, Jin Yeul Ma
Mylabris phalerata (MP) is an insect used in oriental herbal treatments for tumor, tinea infections, and stroke. Recent studies have shown that tumor-associated macrophages (TAM) have detrimental roles such as tumor progression, angiogenesis, and metastasis. Although TAM has phenotypes and characteristics in common with M2-polarized macrophages, M1 macrophages have tumor suppression and immune stimulation effects. Medicines polarizing macrophages to M1 have been suggested to have anticancer effects via the modulation of the tumor microenvironment...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28804691/combination-of-celecoxib-celebrex-%C3%A2-and-cd19-car-redirected-ctl-immunotherapy-for-the-treatment-of-b-cell-non-hodgkin-s-lymphomas
#5
REVIEW
Tam Nm Dinh, Alexandra S Onea, Ali R Jazirehi
The nonsteroidal anti-inflammatory drug (NSAID) Celecoxib (Celebrex(®)) received Food and Drug Administration (FDA) approval in 1998 for treatment of osteoarthritis and rheumatoid arthritis, and in recent years, its use has been extended to various types of malignancies, such as breast, colon, and urinary cancers. To maintain the survival of malignant B cells, non-Hodgkin's Lymphoma (NHL) is highly dependent on inflammatory microenvironment, and is inhibited by celecoxib. Celecoxib hinders tumor growth interacting with various apoptotic genes, such as cyclooxygenase-2 (Cox-2), B-cell lymphoma 2 (Bcl-2) family, phosphor-inositide-3 kinase/serine-threonine-specific protein kinase (PI3K/Akt), and inhibitors of apoptosis proteins (IAP) family...
2017: American Journal of Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28780614/targeting-immune-system-alterations-in-hodgkin-lymphoma
#6
REVIEW
Natalie S Grover, Barbara Savoldo
PURPOSE OF REVIEW: This review discusses novel immunotherapeutic approaches to treat Hodgkin lymphoma (HL), specifically PD-1 inhibitors and cellular immunotherapy. RECENT FINDINGS: PD-1 inhibitors have shown promising results in the treatment of relapsed or refractory HL, leading to FDA approval of nivolumab and pembrolizumab, although complete remissions are rare. Chimeric antigen receptor T cells directed against CD30 have been investigated with preliminary clinical trials showing minimal toxicities and some responses in heavily pre-treated patients with HL...
August 5, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28771673/activity-of-lenalidomide-in-mantle-cell-lymphoma-can-be-explained-by-nk-cell-mediated-cytotoxicity
#7
Patrick R Hagner, Hsiling Chiu, Maria Ortiz, Benedetta Apollonio, Maria Wang, Suzana Couto, Michelle F Waldman, Erin Flynt, Alan G Ramsay, Matthew Trotter, Anita K Gandhi, Rajesh Chopra, Anjan Thakurta
Lenalidomide is an immunomodulatory agent that has demonstrated clinical benefit for patients with relapsed or refractory mantle cell lymphoma (MCL); however, despite this observed clinical activity, the mechanism of action (MOA) of lenalidomide has not been characterized in this setting. We investigated the MOA of lenalidomide in clinical samples from patients enrolled in the CC-5013-MCL-002 trial (NCT00875667) comparing single-agent lenalidomide versus investigator's choice single-agent therapy and validated our findings in pre-clinical models of MCL...
August 2, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28767666/mismatch-repair-deficient-hematopoietic-stem-cells-are-preleukemic-stem-cells
#8
Yulan Qing, Stanton L Gerson
Whereas transformation events in hematopoietic malignancies may occur at different developmental stages, the initial mutation originates in hematopoietic stem cells (HSCs), creating a preleukemic stem cell (PLSC). Subsequent mutations at either stem cell or progenitor cell levels transform the PLSC into lymphoma/leukemia initiating cells (LIC). Thymic lymphomas have been thought to develop from developing thymocytes. T cell progenitors are generated from HSCs in the bone marrow (BM), but maturation and proliferation of T cells as well as T-lymphomagenesis depends on both regulatory mechanisms and microenvironment within the thymus...
2017: PloS One
https://www.readbyqxmd.com/read/28758825/rationale-for-targeting-tumor-cells-in-their-microenvironment-for-mantle-cell-lymphoma-treatment
#9
Antonin Papin, Steven Le Gouill, David Chiron
Mantle cell lymphoma (MCL) is an aggressive non-Hodgkin lymphoma associated with poor prognosis, and despite recent improvements in the therapeutic strategies for treating MCL, its management remains challenging. While improvements in next generation sequencing technology have greatly increased our understanding of the intrinsic abnormalities of MCL, the role of extrinsic signaling remains largely unknown. Recent studies have highlighted the central role of the MCL microenvironment in tumor cell survival, drug resistance and proliferation...
July 31, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28756808/role-of-immune-microenvironmental-factors-for-improving-the-ipi-related-risk-stratification-of-aggressive-b-cell-lymphoma
#10
Yi Gong, Rui Chen, Xi Zhang, Zhong Min Zou, Xing Hua Chen
OBJECTIVE: To investigate the risk stratification of aggressive B cell lymphoma using the immune microenvironment and clinical factors. METHODS: A total of 127 patients with aggressive B cell lymphoma between 2014 and 2015 were enrolled in this study. CD4, Foxp3, CD8, CD68, CD163, PD-1, and PD-L1 expression levels were evaluated in paraffin-embedded lymphoma tissues to identify their roles in the risk stratification. Eleven factors were identified for further evaluation using analysis of variance, chi-square, and multinomial logistic regression analysis...
July 2017: Biomedical and Environmental Sciences: BES
https://www.readbyqxmd.com/read/28753572/vegf121-is-predictor-for-survival-in-activated-b-cell-like-diffuse-large-b-cell-lymphoma-and-is-related-to-an-immune-response-gene-signature-conserved-in-cancers
#11
Julien Broséus, Samia Mourah, Gérard Ramstein, Sophie Bernard, Nicolas Mounier, Wendy Cuccuini, Philippe Gaulard, Christian Gisselbrecht, Josette Brière, Rémi Houlgatte, Catherine Thieblemont
Tumor microenvironment including endothelial and immune cells plays a crucial role in tumor progression and has been shown to dramatically influence cancer survival. In this study, we investigated the clinical relevance of the gene expression of key mediators of angiogenesis, VEGF isoforms 121, 165, and 189, and their receptors (VEGFR-1 and R-2) in a cohort of patients (n = 37) with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) from the Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL)...
July 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28753568/elevated-serum-interleukin-10-level-and-m2-macrophage-infiltration-are-associated-with-poor-survival-in-angioimmunoblastic-t-cell-lymphoma
#12
Jun Soo Ham, Ha Young Park, Kyung Ju Ryu, Young Hyeh Ko, Won Seog Kim, Seok Jin Kim
Interleukin-10 (IL-10) induces an immunosuppressive microenvironment including M2 macrophages, inhibiting anti-tumor immunity. The aim of this study was to evaluate whether serum IL-10 level at diagnosis and tissue infiltration of M2 macrophages could predict survival outcome of patients with angioimmunoblastic T-cell lymphoma (AITL).We measured serum levels of IL-5, IL-10, IL-12, and interferon-gamma (IFN-γ) at diagnosis in AITL and other common subtypes of nodal T-cell lymphoma including peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), ALK-negative anaplastic large cell lymphoma (ALCL) or ALK-positive ALCL between September 2008 and December 2014...
July 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28735665/prevalence-of-foxp3-cells-does-not-correlate-with-ki67-expression-in-canine-diffuse-large-b-cell-lymphoma
#13
C F Muir, S L Priestnall, A Hibbert, C Brown, O A Garden, T Scase
Diffuse large B-cell lymphoma (DLBCL) is the most common type of canine lymphoma and survival times are currently <1 year. Manipulation of the tumour microenvironment, of which the regulatory T cell (Treg) is a principal player, represents a potentially exciting way to curb the rapid proliferation of neoplastic cells. Tregs, characterized by the stable expression of the transcription factor FoxP3, suppress innate and adaptive arms of the immune response and represent a potential therapeutic target within neoplastic lymph nodes...
July 2017: Journal of Comparative Pathology
https://www.readbyqxmd.com/read/28733197/extrafollicular-pd1-and-intrafollicular-cd3-expression-are-associated-with-survival-in-follicular-lymphoma
#14
Kedmi Meirav, Schiby Ginette, Tadmor Tamar, Barshack Iris, Nagler Arnon, Avigdor Abraham
INTRODUCTION: Both microenvironment and tumor biomarkers impact outcome in follicular lymphoma (FL). We aimed to study the effect of Ki-67, CD3, CD68, and PD1 expression on outcome of FL. MATERIALS AND METHODS: Forty-eight patients were included. Stained slides were visually assessed and marker expression was correlated with outcome. Both intra- and extrafollicular expression of Ki-67, CD68, and PD1 were evaluated. CD3 was evaluated only in the intrafollicular area...
June 23, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28725493/interferon-alpha-based-immunotherapies-in-the-treatment-of-b-cell-derived-hematologic-neoplasms-in-today-s-treat-to-target-era
#15
REVIEW
Li Zhang, Yu-Tzu Tai, Matthew Zhi Guang Ho, Lugui Qiu, Kenneth C Anderson
B cell lymphoma and multiple myeloma (MM) are the most common hematological malignancies which benefit from therapeutic monoclonal antibodies (mAbs)-based immunotherapies. Despite significant improvement on patient outcome following the use of novel therapies for the past decades, curative treatment is unavailable for the majority of patients. For example, the 5-year survival of MM is currently less than 50%. In the 1980s, interferon-α was used as monotherapy in newly diagnosed or previously treated MM with an overall response rate of 15-20%...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28719907/tumor-heterogeneity-in-lymphomas-a-different-breed
#16
Christian M Schürch, Birgit Federmann, Leticia Quintanilla-Martinez, Falko Fend
The facts that cancer represents tissues consisting of heterogeneous neoplastic, as well as reactive, cell populations and that cancers of the same histotype may show profound differences in clinical behavior have long been recognized. With the advent of new technologies and the demands of precision medicine, the investigation of tumor heterogeneity has gained much interest. An understanding of intertumoral heterogeneity in patients with the same disease entity is necessary to optimally guide personalized treatment...
July 19, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28703283/wnt-signaling-pathways-in-chronic-lymphocytic-leukemia-and-b-cell-lymphomas
#17
REVIEW
Pavlína Janovská, Vítězslav Bryja
In this review, we discuss the intricate roles of the WNT signaling network in the development and progression of mature B cell-derived hematological malignancies, with a focus on chronic lymphocytic leukemia (CLL) and related B cell lymphomas. We review the current literature and highlight the differences between the β-catenin-dependent and independent branches of WNT signaling. Special attention is paid to the role of the non-canonical WNT/Planar cell polarity (PCP) pathway, mediated by the WNT5-ROR1-Dishevelled (DVL) signaling axis in CLL...
July 12, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28699226/ebv-provides-survival-factors-to-ebv-dlbcl-lines-and-modulates-cytokine-induced-specific-chemotaxis-in-ebv-dlbcl
#18
Liang Wu, Barbro Ehlin-Henriksson, Xiaoying Zhou, Hong Zhu, Ingemar Ernberg, Lorand L Kis, George Klein
Diffuse large B-cell lymphoma (DLBCL), the most common type of malignant lymphomas, account for 30% of adult non-Hodgkin lymphomas (NHLs). EBV-positive DLBCL of the elderly is a newly recognized subtype that accounts for 8% to 10% of DLBCL in Asian countries, but is less common in Western populations. Five DLBCL derived cell lines were employed to characterize patterns of EBV latent gene expression, as well as response to cytokines and chemotaxis. IL-4 and IL-21 modified LMP1-, EBNA1- and EBNA2-expression depending on cell phenotype and type of EBV latent program (type I, II or III)...
July 12, 2017: Immunology
https://www.readbyqxmd.com/read/28698206/expression-of-pim-kinases-in-reed-sternberg-cells-fosters-immune-privilege-and-tumor-cell-survival-in-hodgkin-lymphoma
#19
Maciej Szydłowski, Monika Prochorec-Sobieszek, Anna Szumera-Cieckiewicz, Edyta Derezinska, Grazyna Hoser, Danuta Wasilewska, Olga Szymanska-Giemza, Ewa Jabłonska, Emilia Białopiotrowicz, Tomasz Sewastianik, Anna Polak, Wojciech Czardybon, Michał Gałezowski, Renata Windak, Jan Maciej Zaucha, Krzysztof Warzocha, Krzysztof Brzózka, Przemysław Juszczynski
Reed-Sternberg (RS) cells of classical Hodgkin lymphoma (cHL) express multiple immunoregulatory proteins that shape the cHL microenvironment and allow tumor cells to evade immune surveillance. Expression of certain immunoregulatory proteins is modulated by pro-survival transcription factors, such as NFκB and STATs. Since these factors also induce expression of the oncogenic PIM1/2/3 serine/threonine kinases, and since PIMs modulate transcriptional activity of NFκB and STATs, we hypothesized that these kinases support RS cell survival and foster their immune privilege...
July 11, 2017: Blood
https://www.readbyqxmd.com/read/28679955/adoptively-transferred-v%C3%AE-9v%C3%AE-2-t-cells-show-potent-antitumor-effects-in-a-preclinical-b-cell-lymphomagenesis-model
#20
Nicholas A Zumwalde, Akshat Sharma, Xuequn Xu, Shidong Ma, Christine L Schneider, James C Romero-Masters, Amy W Hudson, Annette Gendron-Fitzpatrick, Shannon C Kenney, Jenny E Gumperz
A central issue for adoptive cellular immunotherapy is overcoming immunosuppressive signals to achieve tumor clearance. While γδ T cells are known to be potent cytolytic effectors that can kill a variety of cancers, it is not clear whether they are inhibited by suppressive ligands expressed in tumor microenvironments. Here, we have used a powerful preclinical model where EBV infection drives the de novo generation of human B cell lymphomas in vivo, and autologous T lymphocytes are held in check by PD-1/CTLA-4-mediated inhibition...
July 6, 2017: JCI Insight
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