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https://www.readbyqxmd.com/read/29330759/-autoimmune-reactions-to-immune-checkpoint-inhibitors
#1
REVIEW
W Pönisch, R Alten, C Baerwald
Immune checkpoint inhibitors (ICI) have dramatically changed the face of cancer treatment and are gaining in importance. The ICIs have now been approved for the treatment of advanced cancers, including melanoma, non-small-cell and small cell lung cancers, renal cell carcinoma, Hodgkin's lymphoma, head and neck cancers and urothelial carcinoma and further indications are to be expected. The organs most affected by an autoimmune reaction are the intestines, the musculoskeletal system, skin, endocrine organs, the liver and the lungs...
October 2017: Zeitschrift Für Rheumatologie
https://www.readbyqxmd.com/read/29330308/survival-outcomes-of-primary-cutaneous-t-cell-lymphoma-in-hiv-infected-patients-a-national-population-based-study
#2
Jianhong Wang, Rong Liang, Caixia Hao, Xiangxiang Liu, Na Zhang, Xiaohui Duan, Hongjuan Dong, Baoxia Dong, Hongtao Gu, Guangxun Gao, Tao Zhang, Qingxian Bai, Xiequn Chen
This study aimed to investigate clinical characteristics and survival outcomes of primary cutaneous T-cell lymphoma (CTCL) in HIV-infected and non-HIV-infected patients. All data were from the Surveillance, Epidemiology, and End Results program, 1973-2013, of the U.S. National Cancer Institute. Data of 318 HIV-infected patients and 1272 non-HIV-infected patients with primary CTCL were analyzed. Endpoints were overall survival and cancer-specific mortality. Independent variables included demographics, pre-existing malignancy, treatments, and environmental factors...
January 12, 2018: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/29324238/immunization-with-recombinant-flid-confers-protection-against-helicobacter-pylori-infection-in-mice
#3
Amir Ghasemi, Nazanin Mohammad, Josef Mautner, Mehrnaz Taghipour Karsabet, Abolfazl Ardjmand, Rezvan Moniri
Nearly half of the world's population is infected with Helicobacter pylori. Clinical manifestations of this infection range from gastritis and peptic ulcers to gastric adenocarcinoma and lymphoma. Due to the emerging of antibiotic resistant strains and poor patient compliance of the antibiotic therapy, there is increasing interest in the development of a protective vaccine against H. pylori infection. The bacterial protein FliD forms a capping structure on the end of each flagellum which is critical to prevent depolymerization and structural degradation...
January 8, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29322203/program-death-inhibitors-in-classical-hodgkin-s-lymphoma-a-comprehensive-review
#4
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/29320898/did-i-miss-it-discovering-hidden-coexisting-hematological-neoplasms-a-single-institutional-review-of-100-collision-tumors
#5
Evan Himchak, Etan Marks, Yang Shi, Yanhua Wang
A collision tumor is defined as two histologically distinct tumor types identified at the same anatomic site. Hematolymphoid proliferative disorders (HLPDs), which coincide with non-hematological neoplasms, can mimic an immune response and can easily be overlooked as an immune reaction to a solid organ neoplasm, especially when low grade. In order to avoid a delay in the diagnosis of a HLPD during the workup for a non-hematological neoplasm, we identified a cohort of 100 cases with a HLPD diagnosis during the initial workup and treatment of a non-hematological neoplasm, or vice versa...
January 1, 2018: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29316610/development-of-a-deimmunized-bispecific-immunotoxin-ddt2219-against-b-cell-malignancies
#6
Joerg U Schmohl, Deborah Todhunter, Elizabeth Taras, Veronika Bachanova, Daniel A Vallera
Diphtheria toxin (DT) related targeted toxins are effective in cancer treatment, but efficacy diminishes in time because of their immunogenic potential and/or former vaccinations. In order to overcome this limitation for DT2219, a promising bispecific targeted toxin which targets CD19 and CD22, we deimmunized the DT moiety, and thereby developed an exciting improved drug (dDT2219) which still has the potential to sufficiently target B-cell malignancies but also limits clearance because of its reduced immunogenicity...
January 6, 2018: Toxins
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
#7
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/29311309/signaling-by-the-epstein-barr-virus-lmp1-protein-induces-potent-cytotoxic-cd4-and-cd8-t-cell-responses
#8
Il-Kyu Choi, Zhe Wang, Qiang Ke, Min Hong, Yu Qian, Xiujuan Zhao, Yuting Liu, Hye-Jung Kim, Jerome Ritz, Harvey Cantor, Klaus Rajewsky, Kai W Wucherpfennig, Baochun Zhang
The B-lymphotropic Epstein-Barr virus (EBV), pandemic in humans, is rapidly controlled on initial infection by T cell surveillance; thereafter, the virus establishes a lifelong latent infection in the host. If surveillance fails, fatal lymphoproliferation and lymphomagenesis ensue. The initial T cell response consists of predominantly CD8+ cytotoxic T cells and a smaller expansion of CD4+ cells. A major approach to treating EBV-associated lymphomas is adoptive transfer of autologous or allogeneic T cells that are stimulated/expanded on EBV-transformed B cells...
January 8, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29304125/a-purified-fermented-extract-of-triticum-aestivum-has-lymphomacidal-activity-mediated-via-natural-killer-cell-activation
#9
Gustavo A Barisone, Robert T O'Donnell, Yunpeng Ma, Mastewal W Abuhay, Kathleen Lundeberg, Sonia Gowda, Joseph M Tuscano
Non-Hodgkin lymphoma (NHL) affects over 400,000 people in the United States; its incidence increases with age. Treatment options are numerous and expanding, yet efficacy is often limited by toxicity, particularly in the elderly. Nearly 70% patients eventually die of the disease. Many patients explore less toxic alternative therapeutics proposed to boost anti-tumor immunity, despite a paucity of rigorous scientific data. Here we evaluate the lymphomacidal and immunomodulatory activities of a protein fraction isolated from fermented wheat germ...
2018: PloS One
https://www.readbyqxmd.com/read/29301940/the-nlr-family-pyrin-domain-containing-11-protein-contributes-to-the-regulation-of-inflammatory-signalling
#10
Kornelia Ellwanger, Emily Becker, Ioannis Kienes, Anna Sowa, Yvonne Postma, Yamel Cardona Gloria, Alexander N R Weber, Thomas A Kufer
Mammalian NLR proteins contribute to the regulation and induction of innate and adaptive immunity in mammals although the function of about half of the currently identified NLR proteins remains poorly characterized. Here we analysed the function of the primate-specific NLRP11 gene product. We show that NLRP11 is highly expressed in immune cells, including myeloid cells, B cells and some B cell lymphoma lines. Overexpression of NLRP11 in human cells did not trigger key innate immune signalling pathways including NF-κB and type I interferon responses...
January 4, 2018: Journal of Biological Chemistry
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
#11
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/29299134/proteomic-changes-in-cerebrospinal-fluid-from-primary-central-nervous-system-lymphoma-patients-are-associated-with-protein-ectodomain-shedding
#12
Daniel Michael Waldera-Lupa, Omid Etemad-Parishanzadeh, Mareike Brocksieper, Nina Kirchgaessler, Sabine Seidel, Thomas Kowalski, Manuel Montesinos-Rongen, Martina Deckert, Uwe Schlegel, Kai Stühler
Primary central nervous system lymphomas (PCNSLs) are mature B-cell lymphomas confined to the central nervous system (CNS). Blood-brain barrier (BBB) dysfunction drastically alters the cerebrospinal fluid (CSF) proteome in PCNSL patients. To reveal the interaction of PCNSL tumors with CNS structures and the vasculature, we conducted a whole-proteome analysis of CSF from PCNSL patients (n = 17 at initial diagnosis) and tumor-free controls (n = 10) using label-free quantitative mass spectrometry. We identified 601 proteins in the CSF proteome using a one-step approach without further prefractionation, and quantified 438 proteins in detail using the Hi-N method...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29298830/golgi-phosphoprotein-2-is-a-novel-regulator-of-il-12-production-and-macrophage-polarization
#13
Wei Zhang, Hajeong Kim, Jiyang Lv, Na Zhao, Xiaojing Ma
Golgi phosphoprotein 2 (GOLPH2), a widely expressed Golgi type II transmembrane protein, has been implicated in several important physiological and pathological processes, including virus infections, cancer cell proliferation, and metastasis. However, its biological functions and mechanisms, particularly in the immune system, remain highly obscure. In this study, we report the biochemical identification of GOLPH2 from B cell lymphoma culture supernatant and show that the secreted protein could inhibit IL-12 production by dendritic cells (DCs) and IL-12-induced IFN-γ production by activated T cells...
January 3, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29297942/expression-pattern-of-immunosurveillance-related-antigen-in-adult-t-cell-leukemia-lymphoma
#14
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/29296965/infiltration-of-effector-regulatory-t-cells-predicts-poor-prognosis-of-diffuse-large-b-cell-lymphoma-not-otherwise-specified
#15
Shoko Nakayama, Taiji Yokote, Toshikazu Akioka, Nobuya Hiraoka, Uta Nishiwaki, Takuji Miyoshi, Kazuki Iwaki, Ayami Takayama, Yuki Masuda, Jun Hatooka, Mayumi Fujimoto, Yasuichiro Nishimura, Motomu Tsuji
Regulatory T cells (Tregs) specifically express the transcription factor forkhead box P3 (FOXP3) and contribute to tumor progression. FOXP3-positive cells have been recently proven to be heterogeneous in phenotype and function, including effector Tregs (eTregs), naïve Tregs, and non-Tregs, which harbor no suppressive function. Therefore, it is crucial to investigate the "true Treg (eTreg)" population, rather than the entire FOXP3 population, with regards to their effect on tumor immunity. In particular, in diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), FOXP3-positive cells correlated with a better prognosis...
March 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296917/checkpoint-blockade-in-hodgkin-and-non-hodgkin-lymphoma
#16
REVIEW
Reid W Merryman, Philippe Armand, Kyle T Wright, Scott J Rodig
Classical Hodgkin lymphoma (cHL) is characterized by nearly universal genetic alterations in 9p24.1, resulting in constitutive expression of PD-1 ligands. This likely underlies the unique sensitivity of cHL to PD-1 blockade, with response rates of ∼70% in relapsed/refractory disease. There are now numerous clinical trials testing PD-1 inhibitors in earlier stages of treatment and in combination with many other therapies. In general, non-Hodgkin lymphomas (NHLs) do not display a high frequency of 9p24.1 alterations and do not share cHL's vulnerability to PD-1 blockade...
December 12, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296911/developing-t-cell-therapies-for-lymphoma-without-receptor-engineering
#17
REVIEW
Melanie Grant, Catherine M Bollard
T-cell therapy has emerged from the bench for the treatment of patients with lymphoma. Responses to T-cell therapeutics are regulated by multiple factors, including the patient's immune system status and disease stage. Outside of engineering of chimeric antigen receptors and artificial T-cell receptors, T-cell therapy can be mediated by ex vivo expansion of antigen-specific T cells targeting viral and/or nonviral tumor-associated antigens. These approaches are contributing to enhanced clinical responses and overall survival...
December 12, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296864/immune-tolerance-induction-by-nonmyeloablative-haploidentical-hsct-combining-t-cell-depletion-and-posttransplant-cyclophosphamide
#18
Franco Aversa, Esther Bachar-Lustig, Noga Or-Geva, Lucia Prezioso, Sabrina Bonomini, Ilenia Manfra, Alessandro Monti, Chiara Schifano, Yael Zlotnikov-Klionsky, Massimo F Martelli, Gabriella Sammarelli, Maria Sassi, Maurizio Soli, Silvia Giuliodori, Magda Benecchi, Nicola Giuliani, Frank Lohr, Silvia Pratissoli, Yair Reisner
The establishment of safe approaches to attain durable donor-type chimerism and immune tolerance toward donor antigens represents a major challenge in transplantation biology. Haploidentical hematopoietic stem cell transplantation (HSCT) is currently used for cancer therapy either as a T-cell-depleted megadose HSCT following myeloablative conditioning or with T-cell-replete HSCT following nonmyeloablative conditioning (NMAC) and high-dose posttransplant cyclophosphamide (PTCY). The latter approach suffers from a significant rate of chronic graft-versus-host disease (GVHD), despite prolonged immunosuppression...
November 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296835/mutation-load-and-an-effector-t-cell-gene-signature-may-distinguish-immunologically-distinct-and-clinically-relevant-lymphoma-subsets
#19
Christopher R Bolen, Ronald McCord, Sarah Huet, Garrett M Frampton, Richard Bourgon, Fabrice Jardin, Peggy Dartigues, Elizabeth A Punnoose, Edith Szafer-Glusman, Luc Xerri, Pierre Sujobert, Gilles Salles, Jeffrey M Venstrom
Identifying follicular lymphoma (FL) patients with preexisting antitumor immunity will inform precision medicine strategies for novel cancer immunotherapies. Using clinical and genomic data from 249 FL patients, we determined the clinical impact of mutation load and an effector T-cell (Teff) gene signature as proxies for the likelihood of a functional immune response. The FL mutation load estimate varied between 0 and 33 mutations per Mb (median, 6.6), and 92% of FL patients with a high mutation load had high Teff gene expression (P = ...
October 10, 2017: Blood Advances
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
#20
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
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