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B lymphocyte and cancer

Gaochen Lan, Jie Li, Qiaomei Wen, Lin Lin, Libin Chen, Liyu Chen, Xi Chen
Cytotoxic T lymphocyte associated antigen 4 (CTLA-4) serves an important role in inhibiting anti-tumor immune response in the majority of solid tumors. However, a limited number of studies reported the function of CTLA-4 in luminal B HER2-negative breast cancer. Immunohistochemistry was performed to evaluate the expression of tumor and interstitial CTLA-4 in luminal B HER2-negative breast cancer tissues. The percentage of patients with tumor and interstitial CTLA-4+ was 41.2% (42/102) and 46.1% (47/102), respectively...
April 2018: Oncology Letters
Neil H Segal, Aiwu R He, Toshihiko Doi, Ronald Levy, Shailender Bhatia, Michael J Pishvaian, Rossano Cesari, Ying Chen, Craig B Davis, Bo Huang, Aron D Thall, Ajay K Gopal
Purpose: Utomilumab (PF-05082566) is an agonistic mAb that engages the immune costimulatory molecule 4-1BB/CD137. In this first-in-human, phase I, open-label, multicenter, multiple-dose study (NCT01307267) we evaluated safety, tolerability, pharmacokinetics, preliminary clinical activity, and pharmacodynamics of single-agent utomilumab in patients with advanced malignancies. Experimental Design: Dose escalation was based on a standard 3+3 design for doses of utomilumab from 0.006 to 0.3 mg/kg every 4 weeks and a time-to-event continual reassessment method for utomilumab 0...
March 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
C Yuan, Q Wang
PURPOSE: The aim of this study was to determine whether different radiotherapy (RT) fractionation schemes induce disparate effects on lymphocyte and its subsets in breast cancer patients. METHODS: 60 female patients diagnosed with breast cancer were recruited in this study after receiving modified radical mastectomy and were randomly divided into two groups. One group received irradiation at a standard dose of 50 Gy in 25 fractions and the other at a dose of 40...
March 13, 2018: Clinical & Translational Oncology
Laura Aragoneses-Fenoll, Gloria Ojeda, María Montes-Casado, Yeny Acosta-Ampudia, Umberto Dianzani, Pilar Portolés, José M Rojo
Class IA phosphatidylinositol 3-kinase (PI3K) catalytic subunits p110α and p110δ are targets in cancer therapy expressed at high levels in T lymphocytes. The role of p110δ PI3K in normal or pathological immune responses is well established, yet the importance of p110α subunits in T cell-dependent immune responses is not clear. To address this problem, mice with p110α conditionally deleted in CD4+ and CD8+ T lymphocytes (p110α-/- ΔT) were used. p110α-/- ΔT mice show normal development of T cell subsets, but slightly reduced numbers of CD4+ T cells in the spleen...
2018: Frontiers in Immunology
Gwendolyn N Y van Gorkom, Roel G J Klein Wolterink, Catharina H M J Van Elssen, Lotte Wieten, Wilfred T V Germeraad, Gerard M J Bos
Vitamin C or ascorbic acid (AA) is implicated in many biological processes and has been proposed as a supplement for various conditions, including cancer. In this review, we discuss the effects of AA on the development and function of lymphocytes. This is important in the light of cancer treatment, as the immune system needs to regenerate following chemotherapy or stem cell transplantation, while cancer patients are often AA-deficient. We focus on lymphocytes, as these white blood cells are the slowest to restore, rendering patients susceptible to often lethal infections...
March 10, 2018: Antioxidants (Basel, Switzerland)
A Mukherjee, R Russell, Suet-Feung Chin, B Liu, O M Rueda, H R Ali, G Turashvili, B Mahler-Araujo, I O Ellis, S Aparicio, C Caldas, E Provenzano
The integration of genomic and transcriptomic profiles of 2000 breast tumours from the METABRIC [Molecular Taxonomy of Breast Cancer International Consortium] cohort revealed ten subtypes, termed integrative clusters (IntClust/s), characterised by distinct genomic drivers. Central histopathology ( N  = 1643) review was undertaken to explore the relationship between these ten molecular subtypes and traditional clinicopathological features. IntClust subtypes were significantly associated with histological type, tumour grade, receptor status, and lymphocytic infiltration ( p  < 0...
2018: NPJ Breast Cancer
Yongxia Wu, Steven Schutt, Katelyn Paz, Mengmeng Zhang, Ryan P Flynn, David Bastian, M Hanief Sofi, Hung Nguyen, Min Dai, Chen Liu, Ying-Jun Chang, Bruce R Blazar, Xue-Zhong Yu
Chronic graft-versus-host disease (cGVHD) is characterized as autoimmune-like fibrosis and antibody production mediated by pathogenic T-cells and B-cells. MicroRNA (miR)-17-92 influences the survival, differentiation and function of lymphocytes in cancer, infections and autoimmunity. To determine whether miR-17-92 regulates T- and B-cell responses in cGVHD, we generated mice conditionally deficient for miR-17-92 in T-cells, B-cells, or both. Using murine models of allogeneic bone marrow transplantation (allo-BMT), we demonstrate that expression of miR-17-92 in donor T- and B-cells is essential for the induction of both scleroderma and bronchiolitis obliterans in cGVHD...
March 12, 2018: Blood
Junyi Shen, Jun Wen, Chuan Li, Tianfu Wen, Lvnan Yan, Bo Li, Jiayin Yang, Changli Lu
BACKGROUND: Microvascular invasion (MVI) is well established as a negative prognostic factor for hepatocelluar carcinoma (HCC). However, its prognostic value in different subgroups of Barcelona Clinical Liver Cancer (BCLC) stages remains to be elucidated. METHODS: Four hundred fifty-eight MVI-negative and 204 MVI-positive patients who underwent hepatectomy were retrospectively analyzed. After propensity score matching (PSM) analysis, 187 pairs of matched patients were generated...
March 12, 2018: BMC Cancer
Artur Martynov, Gennady Didenko, Boris Farber, Sophya Farber, Olena Cruts
OBJECTIVES: Many adenocarcinomas have the ability to capture from an extracellular matrix the oligonucleotides and nanoparticles by pinocytosis, when the non-cancerous cells are not capable to capture the oligonucleotides and small liposomes. This provides selective accumulation of proposed protected oligonucleotides (fRNA) in cancer cells and also provides the absence toxicity in the fRNA. METHODS: For the immunotherapy, we used immunotropic 70 kDa lectin Bacillus subtilis B-7025...
March 9, 2018: Journal of Pharmacy and Pharmacology
Nadia Khan, Brad Kahl
Resistance to apoptosis is one of the hallmarks of cancer and members of the B-cell lymphoma 2 (BCL-2) family of proteins are central regulators of apoptosis. Many cancers become resistant to chemotherapy and apoptosis by up-regulating BCL-2 and other family members, making these proteins attractive targets for cancer therapy. Venetoclax is an orally administered, small-molecule apoptosis stimulant that targets BCL-2 proteins by acting as a BCL-2 homology domain 3 (BH3) mimetic. The drug is approved in the USA and EU as a monotherapy for the for the treatment of certain patients with chronic lymphocytic leukemia (CLL) and is in phase III clinical development for multiple myeloma (MM), and in phase II or I/II clinical trials for acute myeloid leukemia, and several B-cell malignancies, including diffuse large B-cell lymphoma, Waldenstrom's macroglobulinaemia, follicular lymphoma, and mantle-cell lymphoma...
March 8, 2018: Targeted Oncology
Xiaoling Xie, Weijun Zhou, Yuxing Hu, Yiran Chen, Honghao Zhang, Yuhua Li
The identification and characterization of tumor-associated antigens (TAAs) that generate specific cytotoxic T lymphocytes (CTLs) are vital to the development of cancer immunotherapy. The epidermal growth factor receptor (EGFR) pathway substrate 8 gene (Eps8) is involved in regulating cancer progression and might be an ideal antigen. In this study, we searched for novel human leukocyte antigen (HLA)-A*2402-restricted epitopes derived from the Eps8 protein via the HLA-binding prediction algorithm. Among four candidates, peptides 327 (EFLDCFQKF), 534 (KYAKSKYDF) and 755 (LFSLNKDEL) induced peptide-specific CTLs to secrete higher levels of interferon-gamma (IFN-γ) and showed enhanced cytotoxic activity against malignant cancer cells...
March 7, 2018: Cell Death & Disease
G Pasello, G Zago, F Lunardi, L Urso, I Kern, G Vlacic, F Grosso, M Mencoboni, G L Ceresoli, M Schiavon, F Pezzuto, A Pavan, S E Vuljan, P Del Bianco, P Conte, F Rea, F Calabrese
Background: Tumor immune microenvironment (TME) plays a key role in malignant pleural mesothelioma (MPM) pathogenesis and treatment outcome, supporting a role of immune checkpoint inhibitors as anticancer approach. This study retrospectively investigated TME and PD-L1 expression in naïve MPM cases and their change under chemotherapy. Patients and methods: Diagnostic biopsies of MPM patients were collected from four Italian and one Slovenian cancer centers. Pathological assessment of necrosis, inflammation, grading, and mitosis was performed...
March 5, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Catherine S Grasso, Marios Giannakis, Daniel K Wells, Tsuyoshi Hamada, Xinmeng Jasmine Mu, Michael Quist, Jonathan A Nowak, Reiko Nishihara, Zhi Rong Qian, Kentaro Inamura, Teppei Morikawa, Katsuhiko Nosho, Gabriel Abril-Rodriguez, Charles Connolly, Helena Escuin-Ordinas, Milan S Geybels, William M Grady, Li Hsu, Siwen Hu-Lieskovan, Jeroen R Huyghe, Yeon Joo Kim, Paige E Krystofinski, Mark Dm Leiserson, Dennis J Montoya, Brian B Nadel, Matteo Pellegrini, Colin C Pritchard, Cristina Puig-Saus, Elleanor H Quist, Benjamin J Raphael, Stephen J Salipante, Daniel Sanghoon Shin, Eve Shinbrot, Brian Shirts, Sachet Shukla, Janet L Stanford, Wei Sun, Jennifer Tsoi, Alexander Upfill-Brown, David A Wheeler, Catherine J Wu, Ming Yu, Syed H Zaidi, Jesse M Zaretsky, Stacey B Gabriel, Eric S Lander, Levi A Garraway, Thomas J Hudson, Charles S Fuchs, Antoni Ribas, Shuji Ogino, Ulrike Peters
To understand the genetic drivers of immune recognition and evasion in colorectal cancer (CRC), we analyzed 1,211 CRC primary tumor samples, including 179 classified as microsatellite instability-high (MSI-high). This set includes The Cancer Genome Atlas CRC cohort of 592 samples, completed and analyzed here. MSI-high, a hypermutated, immunogenic subtype of CRC, had a high rate of significantly mutated genes in important immune modulating pathways and in the antigen presentation machinery, including biallelic losses of B2M and HLA genes due to copy number alterations and copy-neutral loss of heterozygosity (CN-LOH)...
March 6, 2018: Cancer Discovery
Keith E Steele, Tze Heng Tan, René Korn, Karma Dacosta, Charles Brown, Michael Kuziora, Johannes Zimmermann, Brian Laffin, Moritz Widmaier, Lorenz Rognoni, Ruben Cardenes, Katrin Schneider, Anmarie Boutrin, Philip Martin, Jiping Zha, Tobias Wiestler
BACKGROUND: Immuno-oncology and cancer immunotherapies are areas of intense research. The numbers and locations of CD8+ tumor-infiltrating lymphocytes (TILs) are important measures of the immune response to cancer with prognostic, pharmacodynamic, and predictive potential. We describe the development, validation, and application of advanced image analysis methods to characterize multiple immunohistochemistry-derived CD8 parameters in clinical and nonclinical tumor tissues. METHODS: Commercial resection tumors from nine cancer types, and paired screening/on-drug biopsies of non-small-cell lung carcinoma (NSCLC) patients enrolled in a phase 1/2 clinical trial investigating the PD-L1 antibody therapy durvalumab (NCT01693562), were immunostained for CD8...
March 6, 2018: Journal for Immunotherapy of Cancer
J-Y Lang, K Ma, J-X Guo, H Sun
OBJECTIVE: B lymphoma is a type of malignant tumor originating from the lymphatic hematopoietic system. The pathogenesis and treatment methods are not clear. The change of oxidative stress is closely related to the cell DNA damage and cell apoptosis, which may be served as a target for cancer treatment. This study aims to illustrate the role of oxidative stress in the regulation of B lymphocytoma. PATIENTS AND METHODS: The tumor tissue was collected from patients with B lymphocytoma...
February 2018: European Review for Medical and Pharmacological Sciences
Juha-Pekka Mattila, Leonardo Mirandola, Maurizio Chiriva-Internati
Although it only accounts for approximately 5% of all female cancer cases, ovarian cancer (OC) ranks as the fifth leading cause of death due to cancer in women. We have evaluated the potential of an orally administered microparticulate vaccine incorporating an immunodominant epitope peptide derived from the cancer/testis antigen sperm protein 17 (SP17) aberrantly expressed in OC, to retard the progression of the disease. The peptide antigen and the immune-stimulatory toll-like receptor 9 ligand CpG oligonucleotide were incorporated into spray dried microparticles composed of enteric and sustained release polymers together with the Aleuria aurantia lectin targeting microfold cells present in the gut-associated lymphoid tissue...
March 4, 2018: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
Q Zhao, Y Li, B Yu, P G Yang, L Q Fan, B B Tan, Y Tian, A B Yang
Objective: To investigate the effect of postoperative precision nutrition therapy on postoperative recovery (PR) of patients with advanced gastric cancer (AGC) after neoadjuvant chemotherapy (NC). Methods: 71 subjects were randomly divided into 2 groups. The 34 patients of research group were treated with postoperative precision nutrition treatment according to the indirect energy measurement method. The 31 patients of control group were treated with traditional postoperative nutrition treatment. All participants were measured for body mass index (BMI), NRS2002, PG-SGA and relevant laboratory test within the 1st day before surgery and 7th day after surgery...
February 23, 2018: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
Rohtesh S Mehta, Katayoun Rezvani
Adoptive cell therapy has emerged as a powerful treatment for advanced cancers resistant to conventional agents. Most notable are the remarkable responses seen in patients receiving autologous CD19-redirected chimeric antigen receptor (CAR) T cells for the treatment of B lymphoid malignancies; however, the generation of autologous products for each patient is logistically cumbersome and has restricted widespread clinical use. A banked allogeneic product has the potential to overcome these limitations, yet allogeneic T-cells (even if human leukocyte antigen-matched) carry a major risk of graft-versus-host disease (GVHD)...
2018: Frontiers in Immunology
Karolin Schneider, Etienne Marbaix, Caroline Bouzin, Marc Hamoir, Pierre Mahy, Vanesa Bol, Vincent Grégoire
BACKGROUND: Human papillomavirus (HPV) prevalence in oropharynx squamous cell carcinoma (OPSCC) is on the rise. HPV-linked OPSCCs represent a distinct clinical entity with a better treatment response and patient survival compared to tumors not linked to HPV. An emerging role in treatment response has been attributed to immune cell infiltration in human tumors. In this study, we investigated immune cell infiltration in human SCC of the head and neck region and its relation to overall survival after treatment with surgery (with or without radiotherapy) or concomitant chemo (or cetuximab)-radiotherapy...
March 1, 2018: Acta Oncologica
Anna Maria Valentini, Federica Di Pinto, Filomena Cariola, Vito Guerra, Gianluigi Giannelli, Maria Lucia Caruso, Michele Pirrelli
Objectives: We investigated the PD-L1 expression in colorectal cancer (CRC) and in its microenvironment. Results: PD-L1 was expressed in neoplastic cells (NCs) and tumor-infiltrating immune cells (IICs). All samples PD-L1+ on NCs were also on IICs. Three types of cancers could be grouped: group A(NCs-/ IICs-); group B (NCs-/ IICs+); group C (NCs+/IICs+). To group A belong tumors characterized by poorly immunogenic competence, poor immune response but massive granulocyte infiltrate, justifying the absence of PD-L1 as an immunoinhibitor receptor...
February 2, 2018: Oncotarget
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