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Microenvironment lymphoma

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https://www.readbyqxmd.com/read/29322203/program-death-inhibitors-in-classical-hodgkin-s-lymphoma-a-comprehensive-review
#1
REVIEW
Reyad Dada
Cancer cells are able to induce immune system tolerance through different mechanisms. Recent achievements in the understanding of tumor microenvironment, invasion, and metastasizing have contributed to accelerated drug developments and approvals. Hodgkin lymphoma (HL) cells are the minority in a lymphocyte-rich microenvironment of HL tissue. The program death-1 (PD-1)/PD-ligand-1 checkpoint is one of the known effective pathways in classical HL to escape the immune system cells. The approval of PD-1 inhibitors in different cancer types with exciting response rates is truly revolutionizing our treatment armamentarium against cancer in general and classical HL in specific...
January 10, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29315015/tumor-specific-t-cells-engineered-to-overcome-tumor-immune-evasion-induce-clinical-responses-in-patients-with-relapsed-hodgkin-lymphoma
#2
Catherine M Bollard, Tamara Tripic, Conrad Russell Cruz, Gianpietro Dotti, Stephen Gottschalk, Vicky Torrano, Olga Dakhova, George Carrum, Carlos A Ramos, Hao Liu, Meng-Fen Wu, Andrea N Marcogliese, Cecilia Barese, Youli Zu, Daniel Y Lee, Owen O'Connor, Adrian P Gee, Malcolm K Brenner, Helen E Heslop, Cliona M Rooney
Purpose Transforming growth factor-β (TGF-β) production in the tumor microenvironment is a potent and ubiquitous tumor immune evasion mechanism that inhibits the expansion and function of tumor-directed responses; therefore, we conducted a clinical study to discover the effects of the forced expression of a dominant-negative TGF-β receptor type 2 (DNRII) on the safety, survival, and activity of infused tumor-directed T cells. Materials and Methods In a dose escalation study, eight patients with Epstein Barr virus-positive Hodgkin lymphoma received two to 12 doses of between 2 × 107 and 1...
January 9, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29308325/eosinophils-the-unsung-heroes-in-cancer
#3
REVIEW
Gilda Varricchi, Maria Rosaria Galdiero, Stefania Loffredo, Valeria Lucarini, Giancarlo Marone, Fabrizio Mattei, Gianni Marone, Giovanna Schiavoni
Prolonged low-grade inflammation or smoldering inflammation is a hallmark of a cancer. Eosinophils are components of the immune microenvironment that modulates tumor initiation and progression. Although canonically associated with a detrimental role in allergic disorders, these cells can induce a protective immune response against helminthes, viral and bacterial pathogens. Eosinophils are a source of anti-tumorigenic (e.g., TNF-α, granzyme, cationic proteins, and IL-18) and protumorigenic molecules (e.g., pro-angiogenic factors) depending on the milieu...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29301121/association-of-soluble-interleukin-2-receptor-and-c-reactive-protein-with-the-efficacy-of-bendamustine-salvage-treatment-for-indolent-lymphomas-and-mantle-cell-lymphoma
#4
Yukiko Kawaguchi, Tsuyoshi Nakamaki, Maasa Abe, Yuta Baba, So Murai, Megumi Watanuki, Nana Arai, Shun Fujiwara, Nobuyuki Kabasawa, Hiroyuki Tsukamoto, Yui Uto, Hirotsugu Ariizumi, Kouji Yanagisawa, Norimichi Hattori, Hiroshi Harada, Bungo Saito
Bendamustine has demonstrated favourable efficacy in relapsed or refractory indolent lymphoma and mantle cell lymphoma. We retrospectively evaluated the pre-treatment clinical and laboratory factors and their correlation with the clinical outcome of these lymphomas. We analysed 53 patients who had been treated with bendamustine alone (n = 6) or rituximab plus bendamustine (n = 47). The overall response rate was 81.1%, with a complete response (CR) rate of 39.6%. The CR rate was significantly low in patients who had elevated levels of soluble interleukin-2 receptor (p = 0...
January 5, 2018: Acta Haematologica
https://www.readbyqxmd.com/read/29297942/expression-pattern-of-immunosurveillance-related-antigen-in-adult-t-cell-leukemia-lymphoma
#5
Naoko Asano, Hiroaki Miyoshi, Takeharu Kato, Joji Shimono, Noriaki Yoshida, Daisuke Kurita, Yuya Sasaki, Keisuke Kawamoto, Koichi Ohshima, Masao Seto
AIMS: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy with a poor prognosis. Human leukocyte antigen (HLA) and β2M serve as key molecules in tumor immunity, and their expression is frequently reduced in tumor cells. Programmed cell death (PD)-1/PD-ligand1 (PD-L1) interactions play a role in escape of tumor cells from T-cell immunity. Therefore, this study aimed to determine the clinicopathological relevance of HLA and β2M expressions in ATLL cells and PD-L1 expression in lymphoma or stromal cells and predict the overall survival of patients with ATLL...
January 3, 2018: Histopathology
https://www.readbyqxmd.com/read/29296784/high-proportions-of-pd-1-and-pd-l1-leukocytes-in-classical-hodgkin-lymphoma-microenvironment-are-associated-with-inferior-outcome
#6
Peter Hollander, Peter Kamper, Karin Ekstrom Smedby, Gunilla Enblad, Maja Ludvigsen, Julie Mortensen, Rose-Marie Amini, Stephen Hamilton-Dutoit, Francesco d'Amore, Daniel Molin, Ingrid Glimelius
Immune checkpoint inhibition targeting the programmed death receptor (PD)-1 pathway is a novel treatment approach in relapsed and refractory classical Hodgkin lymphoma (cHL). Identifying patients with a high risk of treatment failure could support the use of PD-1 inhibitors as front-line treatment. Our aim was to investigate the prognostic impact of PD-1, programmed death-ligand 1 (PD-L1), and PD-L2 in the tumor microenvironment in diagnostic biopsies of patients with cHL. Patients from Denmark and Sweden, diagnosed between 1990 and 2007 and ages 15 to 86 years, were included...
August 8, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296775/th17-immune-microenvironment-in-epstein-barr-virus-negative-hodgkin-lymphoma-implications-for-immunotherapy
#7
Amy S Duffield, Maria Libera Ascierto, Robert A Anders, Janis M Taube, Alan K Meeker, Shuming Chen, Tracee L McMiller, Neil A Phillips, Haiying Xu, Aleksandra Ogurtsova, Alan E Berger, Drew M Pardoll, Suzanne L Topalian, Richard F Ambinder
Classical Hodgkin lymphoma (CHL) is a neoplasm characterized by robust inflammatory infiltrates and heightened expression of the immunosuppressive PD-1/PD-L1 pathway. Although anti-PD-1 therapy can be effective in >60% of patients with refractory CHL, improved treatment options are needed for CHLs which are resistant to anti-PD-1 or relapse after this form of immunotherapy. A deeper understanding of immunologic factors in the CHL microenvironment might support the design of more effective treatment combinations based on anti-PD-1...
July 25, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296768/patient-derived-xenografts-of-low-grade-b-cell-lymphomas-demonstrate-roles-of-the-tumor-microenvironment
#8
W Richard Burack, Janice M Spence, John P Spence, Stephen A Spence, Philip J Rock, Gautam N Shenoy, Leonard D Shultz, Richard B Bankert, Steven H Bernstein
To discern features of non-Hodgkin lymphomas (NHL) that are autonomous from those that are shaped by the tumor environment (TE), we used patient-derived xenografts (PDX) to probe the effects on neoplastic cells of manipulating the TE. Properties of neoplastic cells that are often considered to be autonomous include their relative independence from stromal support, their relative survival and/or proliferation advantages compared with nonneoplastic cells, and their state of differentiation. Prior approaches to creation of PDX models likely select for neoplasms, which are the most capable of engraftment, potentially masking the effects of the TE...
July 11, 2017: Blood Advances
https://www.readbyqxmd.com/read/29248547/dual-role-of-ezh2-in-cutaneous-anaplastic-large-cell-lymphoma-promoting-tumor-cell-survival-and-regulating-tumor-microenvironment
#9
Shengguo Yi, Jingru Sun, Lei Qiu, Wenjing Fu, Anqi Wang, Xiaoqing Liu, Yong Yang, Marshall E Kadin, Ping Tu, Yang Wang
Primary cutaneous anaplastic T cell lymphoma (PCALCL), characterized by the CD30+ anaplastic large T cells, comprises the second most common group of cutaneous T-cell lymphoma (CTCL). Little is known about the mechanisms of disease progression. Here we report that enhancer of zeste homolog 2 (EZH2), the catalytic subunit of polycomb repressive complex 2 (PRC2) which mediates histone H3 lysine 27 trimethylation (H3K27me3), is over-expressed in CD30+ anaplastic cells in PCALCL and large-cell transformed CTCL...
December 14, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29248133/hodgkin-lymphoma-a-complex-metabolic-ecosystem-with-glycolytic-reprogramming-of-the-tumor-microenvironment
#10
Lekha Mikkilineni, Diana Whitaker-Menezes, Marina Domingo-Vidal, John Sprandio, Paola Avena, Paolo Cotzia, Alina Dulau-Florea, Jerald Gong, Guldeep Uppal, Tingting Zhan, Benjamin Leiby, Zhao Lin, Barbara Pro, Federica Sotgia, Michael P Lisanti, Ubaldo Martinez-Outschoorn
BACKGROUND: Twenty percent of patients with classical Hodgkin Lymphoma (cHL) have aggressive disease defined as relapsed or refractory disease to initial therapy. At present we cannot identify these patients pre-treatment. The microenvironment is very important in cHL because non-cancer cells constitute the majority of the cells in these tumors. Non-cancer intra-tumoral cells, such as tumor-associated macrophages (TAMs) have been shown to promote tumor growth in cHL via crosstalk with the cancer cells...
June 2017: Seminars in Oncology
https://www.readbyqxmd.com/read/29246182/expression-and-clinical-value-of-programmed-cell-death-ligand-1-pd-l1-in-diffuse-large-b-cell-lymphoma-a-retrospective-study
#11
Li-Yang Hu, Xiao-Lu Xu, Hui-Lan Rao, Jie Chen, Ren-Chun Lai, Hui-Qiang Huang, Wen-Qi Jiang, Tong-Yu Lin, Zhong-Jun Xia, Qing-Qing Cai
BACKGROUND: The programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway inhibits the activation of T cells and plays a crucial role in the negative regulation of cellular and humoral immune responses. Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults. In the present study, we aimed to detect the expression of PD-L1 in DLBCL and to analyze its relationship with prognosis. METHODS: We reviewed medical records of 204 newly diagnosed DLBCL patients in Sun Yat-sen University Cancer Center between October 2005 and August 2012...
December 16, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/29238954/il-25-is-involved-in-ctcl-progression-by-establishing-th2-dominant-microenvironment
#12
R Nakajima, T Miyagaki, T Oka, N Takahashi, M Hirakawa, H Suga, A Yoshizaki, H Fujita, Y Asano, M Sugaya, S Sato
BACKGROUND: Interleukin (IL)-25 is a member of the IL-17 family which can promote and augment T-helper type (Th) 2 responses. The expression of IL-25 and its cognate receptor, IL-25 receptor (IL-25R), is upregulated and correlated with disease activity in Th2-associated diseases. OBJECTIVE: To examine the expression and function of IL-25 in cutaneous T-cell lymphoma (CTCL). METHODS: Expression and localization of IL-25 in lesional skin was investigated using immunohistochemistry...
December 13, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/29235095/immune-cells-regulate-vegf-signaling-via-release-of-vegf-and-antagonistic-soluble-vegf-receptor-1
#13
Timm Hoeres, Martin Wilhelm, Manfred Smetak, Elisabeth Holzmann, Gundula Schulze-Tanzil, Josef Birkmann
Vascular endothelial growth factor (VEGF) is an important regulator of physiological and pathological angiogenesis. Beside malignant and stromal cells, local immune cells shape VEGF signaling in the tumor microenvironment. Aminobisphosphonates like zoledronic acid (Zol) are drugs known to inhibit osteoclast activity and bone resorption, but also have immunomodulatory and anti-tumor effects. These properties have previously been linked to the downregulation of VEGF and interference with tumor neo-angiogenesis...
December 13, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29222312/harnessing-the-power-of-the-immune-system-in-non-hodgkin-lymphoma-immunomodulators-checkpoint-inhibitors-and-beyond
#14
REVIEW
Stephen M Ansell
Non-Hodgkin lymphoma is a malignancy of B lymphocytes that typically infiltrate sites of disease, including the lymph nodes, spleen, and bone marrow. Beyond the presence of malignant cells, many immune cells are also present within the tumor microenvironment. Although these immune cells have the potential to regulate the growth of malignant B cells, intratumoral immune cells are unable to eradicate lymphoma cells and most patients with lymphoma have clinical evidence of disease progression. Recent data have identified some of the mechanisms that account for the suppressed antitumor immune response and have created opportunities for treatment to overcome the deficiencies...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222311/role-of-the-microenvironment-across-histological-subtypes-of-nhl
#15
REVIEW
Karin Tarte
Recent progress in next-generation sequencing strategies has revealed the genetic landscape of B-cell non-Hodgkin lymphoma, but the tumor microenvironment is increasingly recognized as crucial to sustaining malignant B-cell survival and growth, subclonal evolution, and drug resistance. The tumor niche is made up of a dynamic and organized network of strongly heterogeneous immune and stromal cell subsets characterized by specific phenotypic, transcriptomic, and functional features. Nonmalignant cell recruitment and plasticity are dictated by lymphoma B cells, which convert their surrounding microenvironment into a supportive niche...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222306/therapy-of-primary-cns-lymphoma-role-of-intensity-radiation-and-novel-agents
#16
REVIEW
Andrés José María Ferreri
Primary central nervous system (CNS) lymphomas represent a subgroup of malignancies with specific characteristics, an aggressive course, and unsatisfactory outcome in contrast with other lymphomas comparable for tumor burden and histological type. Despite the high sensitivity to conventional chemotherapy and radiotherapy, remissions are frequently short lasting. Treatment efficacy is limited by several factors, including the biology and microenvironment of this malignancy and the "protective" effect of the blood-brain barrier, which limits the access of most drugs to the CNS...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222305/biology-of-cns-lymphoma-and-the-potential-of-novel-agents
#17
REVIEW
James L Rubenstein
Primary and secondary CNS lymphomas are aggressive brain tumors that pose an immense challenge to define in terms of molecular pathogenesis, as well as to effectively treat. During the past 10 years improvements in survival have been achieved with the implementation of anti-CD20 immunotherapy and optimization of dose-intensive consolidation strategies. The applications of whole-exome sequencing, comparative genomic hybridization, transcriptional profiling, and examination of the tumor microenvironment, particularly in the context of clinical investigation, provide insights that create a roadmap for the development and implementation of novel targeted agents for this disease...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222272/signaling-pathways-and-immune-evasion-mechanisms-in-classical-hodgkin-lymphoma
#18
REVIEW
W Robert Liu, Margaret A Shipp
Classical Hodgkin lymphoma (cHL) is an unusual B-cell-derived malignancy in which rare malignant Hodgkin and Reed-Sternberg (HRS) cells are surrounded by an extensive but ineffective inflammatory/immune cell infiltrate. This striking feature suggests that malignant HRS cells escape immunosurveillance and interact with immune cells in the cancer microenvironment for survival and growth. We previously found that cHLs have a genetic basis for immune evasion: near-uniform copy number alterations of chromosome 9p24...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29217528/t-cells-expressing-checkpoint-receptor-tigit-are-enriched-in-follicular-lymphoma-tumors-and-characterized-by-reversible-suppression-of-t-cell-receptor-signaling
#19
Sarah E Josefsson, Kanutte Huse, Arne Kolstad, Klaus Beiske, Daniela Pende, Chloé B Steen, Else Marit Inderberg, Ole Christian Lingjærde, Bjørn Østenstad, Erlend B Smeland, Ronald Levy, Jonathan M Irish, June H Myklebust
PURPOSE: T cells infiltrating follicular lymphoma (FL) tumors are considered dysfunctional, yet the optimal target for immune checkpoint blockade is unknown. Characterizing co-inhibitory receptor expression patterns and signaling responses in FL T-cell subsets might reveal new therapeutic targets. EXPERIMENTAL DESIGN: Surface expression of 9 co-inhibitory receptors governing T-cell function was characterized in T-cell subsets from FL lymph node tumors and from healthy donor tonsils and peripheral blood samples, using high-dimensional flow cytometry...
December 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29209918/molecular-classification-and-precision-therapy-of-cancer-immune-checkpoint-inhibitors
#20
Yingyan Yu
On May 23, 2017, the US Food and Drug Administration (FDA) approved a treatment for cancer patients with positive microsatellite instability-high (MSI-H) markers or mismatch repair deficient (dMMR) markers. This approach is the first approved tumor treatment using a common biomarker rather than specified tumor locations in the body. FDA previously approved Keytruda for treatment of several types of malignancies, such as metastatic melanoma, metastatic non-small-cell lung cancer, recurrent or metastatic head and neck cancer, refractory Hodgkin lymphoma, and urothelial carcinoma, all of which carry positive programmed death-1/programmed death-ligand 1 biomarkers...
December 5, 2017: Frontiers of Medicine
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