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B lymphocyte and cancer

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https://www.readbyqxmd.com/read/28436934/biopolymers-codelivering-engineered-t-cells-and-sting-agonists-can-eliminate-heterogeneous-tumors
#1
Tyrel T Smith, Howell F Moffett, Sirkka B Stephan, Cary F Opel, Amy G Dumigan, Xiuyun Jiang, Venu G Pillarisetty, Smitha P S Pillai, K Dane Wittrup, Matthias T Stephan
Therapies using T cells that are programmed to express chimeric antigen receptors (CAR T cells) consistently produce positive results in patients with hematologic malignancies. However, CAR T cell treatments are less effective in solid tumors for several reasons. First, lymphocytes do not efficiently target CAR T cells; second, solid tumors create an immunosuppressive microenvironment that inactivates T cell responses; and third, solid cancers are typified by phenotypic diversity and thus include cells that do not express proteins targeted by the engineered receptors, enabling the formation of escape variants that elude CAR T cell targeting...
April 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28435024/lkb1-deletion-in-murine-b-lymphocytes-promotes-cell-death-and-cancer
#2
George P Souroullas, Yuri Fedoriw, Louis M Staudt, Norman E Sharpless
LKB1 (aka STK11) is a potent tumor suppressor in solid tumors such as melanoma and lung adenocarcinoma, but inactivation in hematopoietic cells causes cell death, without signs of tumorigenesis. We noted somatic LKB1 deletion or mutation at low frequency in human B cell lymphoma. In order to determine if LKB1 inactivation is a passenger or driver event in lymphoid cancers, we examined the effects of conditional inactivation of Lkb1 in murine lymphocytes. Consistent with prior reports, Lkb1 deletion in either T or B cells resulted in massive, lineage-specific apoptosis...
April 20, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28433635/prognostic-significance-and-functional-implication-of-immune-activating-receptor-nkg2d-in-gastric-cancer
#3
Fengjuan Lin, Congqi Dai, Xiaoxiao Ge, Wenbo Tang, Ying Lin, Yan Wang, Jin Li
NKG2D, an activating receptor expressed on CD8(+) T lymphocytes, serves as a co-stimulation molecule by engagement with its ligands MICA/B and ULBPs to trigger immune activation against tumors. Currently, the biological function and clinical significance of NKG2D in gastric cancer remains unexplored. The study aims to investigate the expression of NKG2D in gastric cancer in association with clinical prognosis and its biological function. Real-time PCR was used to analyze NKG2D expression in paired cancer and adjacent non-malignant tissues in 139 gastric cancer patients between 2007 and 2010 in Shanghai Cancer Center...
April 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28430349/prognostic-significance-of-infiltrating-immune-cell-subtypes-in-invasive-ductal-carcinoma-of-the-breast
#4
Yangmei Xu, Suzhen Lan, Qiuhong Zheng
PURPOSE: To explore the correlation between tumor-infiltrating immune cell subsets and breast cancer prognosis. MATERIALS AND METHODS: Specimens of 102 patients with invasive ductal carcinoma of the breast were analyzed for immune-related markers (CD8, CD20, FOXP3 and CD68). The number of positive cells in the 3 most highly stained intratumoral stroma areas of the primary tumor was counted. The mean number was calculated and used to divide patients into 2 groups for each marker (CD8-high/CD8-low, CD20-high/CD20-low, FOXP3-high/FOXP3-low, and CD68-high/CD68-low)...
April 20, 2017: Tumori
https://www.readbyqxmd.com/read/28426105/the-prevalence-and-clinical-relevance-of-tumor-infiltrating-lymphocytes-tils-in-ductal-carcinoma-in-situ-of-the-breast
#5
G Pruneri, M Lazzeroni, V Bagnardi, G B Tiburzio, N Rotmensz, A DeCensi, A Guerrieri-Gonzaga, A Vingiani, G Curigliano, S Zurrida, F Bassi, R Salgado, G Van den Eynden, S Loi, C Denkert, B Bonanni, G Viale
Background: Tumor-infiltrating lymphocytes (TILs) are a robust prognostic adjunct in invasive breast cancer, but their clinical role in ductal carcinoma in situ (DCIS) has not been ascertained. Patients and methods: We evaluated the prevalence and clinical relevance of TILs in a well annotated series of 1488 consecutive DCIS women with a median follow-up of 8.2 years. Detailed criteria for TILs evaluation were pre-defined involving the International Immuno-Oncology Biomarker Working Group...
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28423700/hla-class-i-loss-in-metachronous-metastases-prevents-continuous-t-cell-recognition-of-mutated-neoantigens-in-a-human-melanoma-model
#6
Barbara Schrörs, Silke Lübcke, Volker Lennerz, Martina Fatho, Anne Bicker, Catherine Wölfel, Patrick Derigs, Thomas Hankeln, Dirk Schadendorf, Annette Paschen, Thomas Wölfel
T lymphocytes against tumor-specific mutated neoantigens can induce tumor regression. Also, the size of the immunogenic cancer mutanome is supposed to correlate with the clinical efficacy of checkpoint inhibition. Herein, we studied the susceptibility of tumor cell lines from lymph node metastases occurring in a melanoma patient over several years towards blood-derived, neoantigen-specific CD8+ T cells. In contrast to a cell line established during early stage III disease, all cell lines generated at later time points from stage IV metastases exhibited partial or complete loss of HLA class I expression...
March 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421677/mindfulness-and-its-efficacy-for-psychological-and-biological-responses-in-women-with-breast-cancer
#7
Elisabeth Kenne Sarenmalm, Lena B Mårtensson, Bengt A Andersson, Per Karlsson, Ingrid Bergh
Many breast cancer survivors have to deal with a variety of psychological and physiological sequelae including impaired immune responses. The primary purpose of this randomized controlled trial was to determine the efficacy of a mindfulness-based stress reduction (MBSR) intervention for mood disorders in women with breast cancer. Secondary outcomes were symptom experience, health status, coping capacity, mindfulness, posttraumatic growth, and immune status. This RTC assigned 166 women with breast cancer to one of three groups: MBSR (8 weekly group sessions of MBSR), active controls (self-instructing MBSR) and non-MBSR...
April 18, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28420814/cell-adhesion-molecule-1-cadm1-expressed-on-adult-t-cell-leukemia-lymphoma-cells-is-not-involved-in-the-interaction-with-macrophages
#8
Yoshihiro Komohara, Chaoya Ma, Hiromu Yano, Cheng Pan, Hasita Horlad, Yoichi Saito, Koji Ohnishi, Yukio Fujiwara, Yutaka Okuno, Kisato Nosaka, Shunsuke Shimosaki, Kazuhiro Morishita, Masao Matsuoka, Tomohiko Wakayama, Motohiro Takeya
Cell adhesion molecule 1 (CADM1) is a cell adhesion molecule that is expressed in brain, liver, lung, testis, and some kinds of cancer cells including adult T-cell leukemia/lymphoma (ATLL). Recent studies have indicated the involvement of CADM1 in cell-cell contact between cytotoxic T-lymphocytes and virus infected cells. We previously reported that cell-cell interaction between lymphoma cells and macrophages induces lymphoma cell proliferation. In the present study, we investigated whether CADM1 is associated with cell-cell interaction between several human lymphoma cell lines and macrophages...
April 18, 2017: Journal of Clinical and Experimental Hematopathology: JCEH
https://www.readbyqxmd.com/read/28419993/reduction-in-peripheral-cd19-cd24hcd27-b-cell-frequency-predicts-favourable-clinical-course-in-xelox-treated-patients-with-advanced-gastric-cancer
#9
Wei Li, Dongli Song, Hong Li, Li Liang, Naiqing Zhao, Tianshu Liu
BACKGROUND: Accumulating evidence suggests that regulatory B cells (Bregs) play an important role in modulating the immune response to tumours. Our previous study indicated that a small percentage of peripheral CD19+CD24hCD27+ Breg cells slowed gastric cancer progression in XELOX-treated patients. Here, we further investigated the relationship between dynamic changes in circulating Breg cells and the clinical course in XELOX-treated gastric cancer patients. METHODS: A total of 52 patients with advanced gastric cancer were enrolled in this study...
April 14, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28419476/cortactin-a-lyn-substrate-is-a-checkpoint-molecule-at-the-intersection-of-bcr-and-cxcr4-signalling-pathway-in-chronic-lymphocytic-leukaemia-cells
#10
Veronica Martini, Cristina Gattazzo, Federica Frezzato, Valentina Trimarco, Marco Pizzi, Giorgia Chiodin, Filippo Severin, Edoardo Scomazzon, Vincenza Guzzardo, Deborah Saraggi, Flavia Raggi, Leonardo Martinello, Monica Facco, Andrea Visentin, Francesco Piazza, Anna Maria Brunati, Gianpietro Semenzato, Livio Trentin
Cortactin (CTTN) is a substrate of the Src kinase Lyn that is known to play an actin cytoskeletal regulatory role involved in cell migration and cancer progression following its phosphorylation at Y421. We recently demonstrated that Cortactin is overexpressed in patients with chronic lymphocytic leukaemia (CLL). This work was aimed at defining the functional role of Cortactin in these patients. We found that Cortactin is variably expressed in CLL patients both in the peripheral blood and lymph nodes and that its expression correlates with the release of matrix metalloproteinase 9 (MMP-9) and the motility of neoplastic cells...
April 17, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28418996/mobilizing-immune-cells-with-exercise-for-cancer-immunotherapy
#11
Richard J Simpson, Austin B Bigley, Nadia Agha, Patrick J Hanley, Catherine M Bollard
Hematopoietic stem cell (HSC) transplantation and adoptive transfer immunotherapy are effective in treating blood cancers and post-transplant infections, but low circulating cell numbers in patients and donors is oftentimes a limiting factor. We postulate that a single exercise bout will increase the yield of patient and donor-derived HSC's and cytotoxic lymphocytes to improve this form of treatment for cancer patients.
April 17, 2017: Exercise and Sport Sciences Reviews
https://www.readbyqxmd.com/read/28418870/neutrophil-to-lymphocyte-ratio-as-prognostic-indicator-in-gastrointestinal-cancers-a-systematic-review-and-meta-analysis
#12
Randy C Bowen, Nancy Ann B Little, Joshua R Harmer, Junjie Ma, Luke G Mirabelli, Kyle D Roller, Andrew Mackay Breivik, Emily Signor, Alec B Miller, Hung T Khong
An accurate, time efficient, and inexpensive prognostic indicator is needed to reduce cost and assist with clinical decision making for cancer management. The neutrophil-to-lymphocyte ratio (NLR), which is derived from common serum testing, has been explored in a variety of cancers. We sought to determine its prognostic value in gastrointestinal cancers and performed a meta-analysis of published studies using the Meta-analysis Of Observational Studies in Epidemiology guidelines. Included were randomized control trials and observational studies that analyzed humans with gastrointestinal cancers that included NLR and hazard ratios (HR) with overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and/or cancer-specific survival (CSS)...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418653/synthesis-and-biological-evaluation-of-the-first-triple-inhibitors-of-human-topoisomerase-1-tyrosyl-dna-phosphodiesterase-1-tdp1-and-tyrosyl-dna-phosphodiesterase-2-tdp2
#13
Ping Wang, Mohamed S A Elsayed, Caroline B Plescia, Azhar Ravji, Christophe E Redon, Evgeny Kiselev, Christophe Marchand, Olga Zeleznik, Keli Agama, Yves Pommier, Mark Cushman
Tdp1 and Tdp2 are two tyrosyl-DNA phosphodiesterases that can repair damaged DNA resulting from topoisomerase inhibitors and a variety of other DNA-damaging agents. Both Tdp1 and Tdp2 inhibition could hypothetically potentiate the cytotoxicities of topoisomerase inhibitors. This study reports the successful structure-based design and synthesis of new 7-azaindenoisoquinolines that act as triple inhibitors of Top1, Tdp1, and Tdp2. Enzyme inhibitory data and cytotoxicity data from human cancer cell cultures establish that modification of the lactam side chain of the 7-azaindenoisoquinolines can modulate their inhibitory potencies and selectivities vs Top1, Tdp1, and Tdp2...
April 18, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28416578/quantitative-mass-spectrometry-analysis-of-pd-l1-protein-expression-n-glycosylation-and-expression-stoichiometry-with-pd-1-and-pd-l2-in-human-melanoma
#14
Carlos A Morales-Betanzos, Hyoungjoo Lee, Paula I Gonzalez-Ericsson, Justin M Balko, Douglas B Johnson, Lisa J Zimmerman, Daniel C Liebler
Quantitative assessment of key proteins that control the tumor-immune interface is one of the most formidable analytical challenges in immunotherapeutics. We developed a targeted mass spectrometry (MS) platform to quantify programmed cell death-1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), and programmed cell death 1 ligand 2 (PD-L2) at fmol/microgram protein levels in formalin fixed, paraffin-embedded sections from 22 human melanomas. PD-L1 abundance ranged 50-fold, from approximately 0.03 to 1.5 fmol/microgram protein and the PRM data were largely concordant with total PD-L1-positive cell content, as analyzed by immunohistochemistry (IHC) with the E1L3N antibody...
April 17, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28415597/phosphorylation-of-androgen-receptors-at-serine-515-is-a-potential-prognostic-marker-for-triple-negative-breast-cancer
#15
Antonia K Roseweir, Pamela McCall, Alison Scott, Benjamin Liew, Zhi Lim, Elizabeth A Mallon, Joanne Edwards
1.7 million cases of breast cancer are diagnosed every year with 522,000 deaths. Molecular classifications of breast cancer have resulted in improved treatments. However, treatments for triple negative breast cancer (TNBC) are lacking. Analysis of molecular targets for TNBC is a priority. One potential candidate is androgen receptor (AR) phosphorylation. This study assessed the role of AR phosphorylation at ser81/ser515 and their two upstream effectors, cyclin-dependent kinase 1 (pCDK1) and extracellular-regulated kinase 1/2 (pERK1/2) in 332 ductal breast cancer patients by immunohistochemistry...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414560/aloe-arborescens-polysaccharides-in-vitro-immunomodulation-and-potential-cytotoxic-activity
#16
Jilan A Nazeam, Haidy A Gad, Ahmed Esmat, Hala M El-Hefnawy, Abdel-Naser B Singab
Different polysaccharides were isolated from the leaves of Aloe arborescens using the gradient power of hydrogen followed by antitumor and immunomodulatory assay. The total polysaccharide content of different fractions, water-soluble polysaccharide (WAP), acid-soluble polysaccharide (ACP), and alkaline-soluble polysaccharide (ALP), was estimated using a phenol-sulfuric acid spectrophotometric method. WAP possessed a higher content of mannose and glucose than either ACP or ALP. In vitro antitumor activity was investigated in three different cancer cell lines, and in vitro immunomodulatory potential was assessed through phagocytosis and lymphocyte transformation assay...
April 17, 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28412730/the-long-noncoding-rna-trerna-decreases-dna-damage-and-is-associated-with-poor-response-to-chemotherapy-in-chronic-lymphocytic-leukemia
#17
Cecelia R Miller, Amy S Ruppert, Sydney Fobare, Timothy L Chen, Chaomei Liu, Amy Lehman, James S Blachly, Xiaoli Zhang, David M Lucas, Michael R Grever, Martin S Tallman, Ian W Flinn, Laura Z Rassenti, Thomas J Kipps, Deepa Sampath, Kevin R Coombes, Erin K Hertlein
The study of long noncoding RNAs (lncRNAs) is an emerging area of cancer research, in part due to their ability to serve as disease biomarkers. However, few studies have investigated lncRNAs in chronic lymphocytic leukemia (CLL). We have identified one particular lncRNA, treRNA, which is overexpressed in CLL B-cells. We measured transcript expression in 144 CLL patient samples and separated samples into high or low expression of treRNA relative to the overall median. We found that high expression of treRNA is significantly associated with shorter time to treatment...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28408486/targeting-ror1-identifies-new-treatment-strategies-in-hematological-cancers
#18
REVIEW
Hanna Karvonen, Wilhelmiina Niininen, Astrid Murumägi, Daniela Ungureanu
Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a member of the ROR receptor family consisting of two closely related type I transmembrane proteins ROR1 and ROR2. Owing to mutations in their canonical motifs required for proper kinase activity, RORs are classified as pseudokinases lacking detectable catalytic activity. ROR1 stands out for its selective and high expression in numerous blood and solid malignancies compared with a minimal expression in healthy adult tissues, suggesting high potential for this molecule as a drug target for cancer therapy...
April 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28408397/the-il-31-il-31-receptor-axis-general-features-and-role-in-tumor-microenvironment
#19
REVIEW
Elisa Ferretti, Anna Corcione, Vito Pistoia
IL-31 is a recently identified cytokine with a well-defined role in the pathogenesis of pruritus. IL-31, whose production is induced by IL-4 and IL-33, binds a heterodimeric receptor (R) composed of the exclusive IL-31RA chain and the shared oncostatin M R. Signaling through the IL-31R involves the MAPK, PI3K/AKT and Jak/STAT pathways. Different variants and isoforms of IL-31RA with different signaling activities have been identified. IL-31 is produced predominantly by circulating Th2 lymphocytes and skin-homing CLA(+)CD45RO(+) T cells...
April 13, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28408386/increased-pd-1-and-tim-3-tils-during-cetuximab-therapy-inversely-correlates-with-response-in-head-and-neck-cancer-patients
#20
Hyun-Bae Jie, Raghvendra M Srivastava, Athanassios Argiris, Julie E Bauman, Lawrence P Kane, Robert L Ferris
Despite emerging appreciation for the important role of immune checkpoint receptors in regulating the effector functions of T cells, it is unknown whether their expression is involved in determining the clinical outcome in response to cetuximab therapy. We examined the expression patterns of immune checkpoint receptors (including PD-1, CTLA-4, and TIM-3) and cytolytic molecules (including granzyme B and perforin) of CD8+ tumorinfiltrating lymphocytes (TILs) and compared them to those of peripheral blood T lymphocytes (PBLs) in patients with head and neck cancer (HNSCC) during cetuximab therapy...
April 13, 2017: Cancer Immunology Research
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