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Microenvironment lymphoma

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https://www.readbyqxmd.com/read/29135607/targeting-the-perivascular-niche-in-brain-tumors
#1
Giorgio Seano
PURPOSE OF REVIEW: Brain tumors are composed of primary tumors of the central nervous system, such us glioblastoma (GBM), and secondary metastatic tumors, such as melanoma, non-Hodgkin lymphoma as well as lung and breast cancers. Brain tumors are highly deadly, and unfortunately not many improvements have been achieved to improve the survival of patients with brain tumors. Chemoradiation resistance is one of the most clinically relevant challenges faced in patients with brain tumors. The perivascular niche is one of the most relevant microenvironment hubs in brain tumors...
November 14, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/29128997/pd-1-pd-l1-immune-checkpoint-blockade-in-malignant-lymphomas
#2
REVIEW
Yi Wang, Ling Wu, Chen Tian, Yizhuo Zhang
Tumor cells can evade immune surveillance through overexpressing the ligands of checkpoint receptors on tumor cells or adjacent cells, leading T cells to anergy or exhaustion. Growing evidence of the interaction between tumor cells and microenvironment promoted the emergence of immune-checkpoint blockade. By targeting programmed cell death-1 (PD-1) pathway, cytotoxic activity of T cell is enhanced significantly and tumor cell lysis is induced subsequently. Currently, various antibodies against PD-1 and programmed death-ligand 1 (PD-L1) are under clinical studies in lymphomas...
November 11, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29127109/incb040093-is-a-novel-pi3k%C3%AE-inhibitor-for-the-treatment-of-b-cell-lymphoid-malignancies
#3
Niu Shin, Yun-Long Li, Song Mei, Kathy He Wang, Leslie Hall, Kamna Katiyar, Qian Wang, Gengjie Yang, Beth Rumberger, Lynn Leffet, Xin He, Mark Rupar, Kevin Bowman, Margaret Favata, Jun Li, Mike Liu, Yanlong Li, Maryanne Covington, Holly Koblish, Maxim Soloviev, Dana Shuey, Timothy Burn, Sharon Diamond, Jordan Fridman, Andrew Combs, Wenqing Yao, Swamy Yeleswaram, Gregory Hollis, Kris Vaddi, Reid Huber, Robert Newton, Peggy Scherle
PI3Kδ is a critical signaling molecule in B cells and is considered a target for development of therapies against various B cell malignancies. INCB040093 is a novel PI3Kδ small molecule inhibitor and has demonstrated promising efficacy in patients with Hodgkin's lymphoma in clinical studies. Here, we disclose the chemical structure and the preclinical activity of the compound. In biochemical assays, INCB040093 potently inhibits the PI3Kδ kinase, with 74 to >900-fold selectivity against other PI3K family members...
November 10, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29118009/immunotherapy-targeting-4-1bb-mechanistic-rationale-clinical-results-and-future-strategies
#4
Cariad Chester, Miguel F Sanmamed, Jun Wang, Ignacio Melero
4-1BB (CD137, TNFRSF9) is an inducible costimulatory receptor expressed on activated T and natural killer (NK) cells. 4-1BB ligation on T cells triggers a signaling cascade that results in upregulation of antiapoptotic molecules, cytokine secretion, and enhanced effector function. In dysfunctional T cells that have a decreased cytotoxic capacity, 4-1BB ligation demonstrates a potent ability to restore effector functions. On NK cells, 4-1BB signaling can increase antibody-dependent cell-mediated cytotoxicity...
November 8, 2017: Blood
https://www.readbyqxmd.com/read/29113197/acidic-stress-induces-apoptosis-and-inhibits-angiogenesis-in-human-bone-marrow-derived-endothelial-progenitor-cells
#5
Shuai Huang, Peiheng He, Dongliang Xu, Jinglei Li, Xinsheng Peng, Yubo Tang
Bone marrow-derived endothelial progenitor cells (BM-EPCs) are exposed to acidotic environments in a variety of physiological and pathological conditions, including in tumors. However, the effect of acidosis on the function of BM-EPCs is still not fully understood. In the present study, BM-EPCs were isolated and cultured at an extracellular pH (pHe) of 6.5 or pHe 7.4 in vitro prior to various experiments being performed. Cellular proliferation, migration and tube formation ability were detected by DNA content quantification, Transwell assay and Matrigel-based angiogenesis assay...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29112015/pd-l1-and-pd-l2-are-differentially-expressed-by-macrophages-or-tumor-cells-in-primary-cutaneous-diffuse-large-b-cell-lymphoma-leg-type
#6
Sarah Menguy, Martina Prochazkova-Carlotti, Marie Beylot-Barry, Fréderic Saltel, Béatrice Vergier, Jean-Philippe Merlio, Anne Pham-Ledard
As checkpoint molecules' inhibition may represent a therapeutic option in relapsing cases, we assessed programmed death ligands' (PD-L1/PD-L2) expression in a series of 29 primary cutaneous diffuse large B-cell lymphoma, leg-type (PCDLBCL-LT) cases. Double immunostaining for either PD-L1 or PD-L2 was associated either with PAX5 staining to evaluate tumor cells or with CD68 or CD163 staining for macrophages. The microenvironment of PCDLBCL-LT was characterized by immunostainings for CD3 (tumor-infiltrating lymphocytes), FOXP3 (regulatory T cells), programmed cell death-1, and CD33 (myeloid-derived suppressor cells)...
November 3, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29100307/elevated-serum-interleukin-10-level-and-m2-macrophage-infiltration-are-associated-with-poor-survival-in-angioimmunoblastic-t-cell-lymphoma
#7
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...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29084248/tti-621-sirp%C3%AE-fc-a-cd47-blocking-cancer-immunotherapeutic-triggers-phagocytosis-of-lymphoma-cells-by-multiple-polarized-macrophage-subsets
#8
Gloria H Y Lin, Vien Chai, Vivian Lee, Karen Dodge, Tran Truong, Mark Wong, Lisa D Johnson, Emma Linderoth, Xinli Pang, Jeff Winston, Penka S Petrova, Robert A Uger, Natasja N Viller
Tumor-associated macrophages (TAMs) are heterogeneous and can adopt a spectrum of activation states between pro-inflammatory and pro-tumorigenic in response to the microenvironment. We have previously shown that TTI-621, a soluble SIRPαFc fusion protein that blocks the CD47 "do-not-eat" signal, promotes tumor cell phagocytosis by IFN-γ-primed macrophages. To assess the impact of CD47 blockade on diverse types of macrophages that are found within the tumor microenvironment, six different polarized human macrophage subsets (M(-), M(IFN-γ), M(IFN-γ+LPS), M(IL-4), M(HAGG+IL-1β), M(IL-10 + TGFβ)) with distinct cell surface markers and cytokine profiles were generated...
2017: PloS One
https://www.readbyqxmd.com/read/29079592/inhibition-of-focal-adhesion-kinase-overcomes-resistance-of-mantle-cell-lymphoma-to-ibrutinib-in-the-bone-marrow-microenvironment
#9
Martina Rudelius, Mathias Tillmann Rosenfeldt, Ellen Leich, Hilka Rauert-Wunderlich, Antonio Giovanni Solimando, Andreas Beilhack, German Ott, Andreas Rosenwald
Mantle cell lymphoma and other lymphoma subtypes often spread to the bone marrow, and stromal interactions mediated by focal adhesion kinase frequently enhance survival and drug resistance of the lymphoma cells. To study the role of focal adhesion kinase in mantle cell lymphoma, immunohistochemistry of primary cases and functional analysis of mantle cell lymphoma cell lines and primary mantle cell lymphoma cells cocultured with bone marrow stromal cells (BMSC) using small molecule inhibitors and RNAi based focal adhesion kinase silencing was performed...
October 27, 2017: Haematologica
https://www.readbyqxmd.com/read/29075266/antibody-or-antibody-fragments-implications-for-molecular-imaging-and-targeted-therapy-of-solid-tumors
#10
Katerina T Xenaki, Sabrina Oliveira, Paul M P van Bergen En Henegouwen
The use of antibody-based therapeutics has proven very promising for clinical applications in cancer patients, with multiple examples of antibodies and antibody-drug conjugates successfully applied for the treatment of solid tumors and lymphomas. Given reported recurrence rates, improvements are clearly still necessary. A major factor limiting the efficacy of antibody-targeted cancer therapies may be the incomplete penetration of the antibody or antibody-drug conjugate into the tumor. Incomplete tumor penetration also affects the outcome of molecular imaging, when using such targeting agents...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29070649/complex-immune-evasion-strategies-in-classical-hodgkin-lymphoma
#11
Frederik Wein, Marc A Weniger, Benedikt Höing, Judith C Arnolds, Andreas Hüttmann, Martin-Leo Hansmann, Sylvia Hartmann, Ralf Küppers
The cellular microenvironment in classical Hodgkin lymphoma (cHL) is dominated by a mixed infiltrate of inflammatory cells with typically only about 1% Hodgkin and Reed/Sternberg (HRS) tumor cells. T cells are usually the largest population of cells in the cHL microenvironment, encompassing T helper (Th) cells, regulatory T (Treg) cells and cytotoxic T cells. Th and Treg cells presumably provide essential survival signals for HRS cells. Treg cells are also involved in rescuing HRS cells from anti-tumor immune responses...
October 25, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29070146/-research-progress-on-molecular-mechanisms-of-resistance-to-bortezomib-in-multiple-myeloma-review
#12
Ling-Ling Shi, Yong-Ping Zhai
Over the last decade, bortezomib(BTZ) has been extensively applied in the treatment of hematological malignancies, particularly in multiple myeloma and mantle cell lymphoma, however, the appearence of secondary resistance to BTZ has brought a huge challenge in MM treatment. In the present review, the mechanisms of resistance to bortezomib in MM are summarized, focusing on the action of ubiquitin-proteasome system(UPS), endoplasmin reticulum stress, antophagy, inducible pro-survival signalling and bone marrow microenvironment as well as exploration of the potential therapeutic strategies in the clinical perspective...
October 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29069828/neutrophils-protect-lymphoma-cells-against-cytotoxic-and-targeted-therapies-through-cd11b-icam-1-binding
#13
Taghreed Hirz, Eva-Laure Matera, Kamel Chettab, Lars Petter Jordheim, Doriane Mathé, Anne Evesque, Justine Esmenjaud, Gilles Salles, Charles Dumontet
Innate immune cells constitute a substantial proportion of the cells within the tumor microenvironment. Besides the contribution of the microenvironment to tumor proliferation and survival, there is direct evidence that interactions between tumor cells and their microenvironment alter sensitivity to anti-cancer agents. Neutrophils, a key player in the innate immune system, have been less studied than many other immune cells regarding their impact on cancer cell response to anti-cancer agents. In our 2D and 3D coculture systems, human neutrophils and differentiated HL60 cells attenuated the sensitivity of various lymphoma cell lines to several anti-cancer agents, including targeted therapies...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29069302/mechanistic-overview-of-immune-checkpoints-to-support-the-rational-design-of-their-combinations-in-cancer-immunotherapy
#14
A Rotte, J Y Jin, V Lemaire
Checkpoint receptor blockers, known to act by blocking the pathways that inhibit immune cell activation and stimulate immune responses against tumor cells, have been immensely successful in the treatment of cancer. Among several checkpoint receptors of immune cells, cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), programmed cell death protein-1 (PD-1), T-cell immunoglobulin and ITIM domain (TIGIT), T-cell immunoglobulin-3 (TIM-3) and lymphocyte activation gene 3 (LAG-3) are the most commonly targeted checkpoints for cancer immunotherapy...
October 24, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29068003/understanding-and-targeting-resistance-mechanisms-in-nsclc
#15
REVIEW
Julia Rotow, Trever G Bivona
The expanding spectrum of both established and candidate oncogenic driver mutations identified in non-small-cell lung cancer (NSCLC), coupled with the increasing number of clinically available signal transduction pathway inhibitors targeting these driver mutations, offers a tremendous opportunity to enhance patient outcomes. Despite these molecular advances, advanced-stage NSCLC remains largely incurable due to therapeutic resistance. In this Review, we discuss alterations in the targeted oncogene ('on-target' resistance) and in other downstream and parallel pathways ('off-target' resistance) leading to resistance to targeted therapies in NSCLC, and we provide an overview of the current understanding of the bidirectional interactions with the tumour microenvironment that promote therapeutic resistance...
October 25, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29067721/the-perivascular-microenvironment-in-epstein-barr-virus-positive-primary-central-nervous-system-lymphoma-the-role-of-programmed-cell-death-1-and-programmed-cell-death-ligand-1
#16
Yasuo Sugita, Takuya Furuta, Koichi Ohshima, Satoru Komaki, Junko Miyoshi, Motohiro Morioka, Hideyuki Abe, Takanori Nozawa, Yukihiko Fujii, Hitoshi Takahashi, Akiyoshi Kakita
It has been shown that high expression of certain immune checkpoint molecules, including those of the programmed death protein 1/programmed death ligand 1 (PD-1/PD-L1) axis, can be utilized to regulate immunosuppression in the microenvironment of malignant neoplasms. For the purpose of clarifying the immune-escape mechanism of primary central nervous system lymphomas (PCNSLs), particularly in Epstein-Barr virus (EBV)-positive cases, markers for PD-1, PD-L1, tumor-associated macrophages (TAMs), and tumor-infiltrating lymphocytes (TILs) in 39 surgical specimens of PCNSLs (17 EBV-positive, 22 EBV-negative) were investigated by immunohistochemistry...
October 24, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/29064587/an-anergic-immune-signature-in-the-tumor-microenvironment-of-classical-hodgkin-lymphoma-is-associated-with-inferior-outcome
#17
Peter Hollander, Klaus Rostgaard, Karin E Smedby, Daniel Molin, Angelica Loskog, Peter de Nully Brown, Gunilla Enblad, Rose-Marie Amini, Henrik Hjalgrim, Ingrid Glimelius
OBJECTIVE: The classical Hodgkin lymphoma (cHL) tumor microenvironment shows an ongoing inflammatory response consisting of varying degrees of infiltrating eosinophils, mast cells, macrophages, regulatory T lymphocytes (Tregs) and activated lymphocytes surrounding the malignant cells. Herein, different immune signatures are characterized and correlated with treatment outcome. METHODS: Tumor-infiltrating leukocytes were phenotyped in biopsies from 459 patients with cHL...
October 24, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/29043381/transformed-follicular-lymphoma
#18
REVIEW
Thais Fischer, Natalia Pin Chuen Zing, Carlos Sergio Chiattone, Massimo Federico, Stefano Luminari
Follicular Lymphoma (FL) is the second most common type of non-Hodgkin lymphoma and is considered to be the prototype of indolent lymphomas. Histologic transformation into an aggressive lymphoma, which is expected to occur at a rate of 2 to 3% each year, is associated with rapid progression, treatment resistance, and poor prognosis. Recent modifications to the physiopathologic mechanism of transformed follicular lymphoma (t-FL) have been proposed, including genetic and epigenetic mechanisms as well as a role for the microenvironment...
October 18, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29032510/current-prognostic-and-predictive-factors-in-follicular-lymphoma
#19
REVIEW
Marc Sorigue, Juan-Manuel Sancho
Follicular lymphoma (FL) is generally considered an indolent disorder. With modern day treatments, long remissions are often achieved both in the front-line and relapsed setting. However, a subset of patients has a more aggressive course and a worse outcome. Their identification is the main purpose of modern day prognostic tools. In this review, we attempt to summarize the evidence concerning prognostic and predictive factors in FL, including (1) pre-treatment factors, from baseline clinical characteristics and imaging tests to histological grade, the microenvironment and genomic abnormalities; (2) post-treatment factors, i...
October 14, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29029511/mesenchymal-stromal-cells-promote-b-cell-lymphoma-in-lacrimal-glands-by-inducing-immunosuppressive-microenvironment
#20
Min Joung Lee, Se Yeon Park, Jung Hwa Ko, Hyun Ju Lee, Jin Suk Ryu, Jong Woo Park, Sang In Khwarg, Sun-Ok Yoon, Joo Youn Oh
Mesenchymal stromal cells (MSCs) have therapeutic potential for various diseases because of their anti-inflammatory and immunosuppressive properties. However, the immunosuppressive microenvironment allows tumor cells to evade immune surveillance, whereas maintenance of inflammation is required for tumor development and progression. Hence, MSCs may promote or suppress tumors in a context-dependent manner. We here investigated the effects of bone marrow-derived MSCs in a murine model of lacrimal gland B-cell lymphoma...
September 12, 2017: Oncotarget
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