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https://www.readbyqxmd.com/read/28651074/chimeric-antigen-receptor-engineered-natural-killer-and-natural-killer-t-cells-for-cancer-immunotherapy
#1
REVIEW
Dominique Bollino, Tonya J Webb
Natural killer (NK) cells of the innate immune system and NK T (NKT) cells, which have roles in both the innate and adaptive responses, are unique lymphocyte subsets that have similarities in their functions and phenotypes. Both cell types can rapidly respond to the presence of tumor cells and participate in immune surveillance and antitumor immune responses. This has incited interest in the development of novel cancer therapeutics based on NK and NKT cell manipulation. Chimeric antigen receptors (CARs), generated through the fusion of an antigen-binding region of a monoclonal antibody or other ligand to intracellular signaling domains, can enhance lymphocyte targeting and activation toward diverse malignancies...
June 9, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28649252/sexual-dimorphic-responses-in-lymphocytes-of-healthy-individuals-after-carica-papaya-consumption
#2
Nur Ramziahrazanah Jumat, Mun Yee Chong, Zainina Seman, Rosita Jamaluddin, Nyet Kui Wong, Maha Abdullah
Sexual dimorphism in immune response is widely recognized, but few human studies have observed this distinction. Food with endo-immunomodulatory potential may reveal novel sex-biased in vivo interactions. Immunomodulatory effects of Carica papaya were compared between healthy male and female individuals. Volunteers were given fixed meals supplemented with papaya for 2 days. Changes in blood immune profiles and hormone levels were determined. In females, total natural killer (NK) cell percentages decreased (12...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28649246/redirected-primary-human-chimeric-antigen-receptor-natural-killer-cells-as-an-off-the-shelf-immunotherapy-for-improvement-in-cancer-treatment
#3
REVIEW
Olaf Oberschmidt, Stephan Kloess, Ulrike Koehl
Primary human natural killer (NK) cells recognize and subsequently eliminate virus infected cells, tumor cells, or other aberrant cells. However, cancer cells are able to develop tumor immune escape mechanisms to undermine this immune control. To overcome this obstacle, NK cells can be genetically modified to express chimeric antigen receptors (CARs) in order to improve specific recognition of cancer surface markers (e.g., CD19, CD20, and ErbB2). After target recognition, intracellular CAR domain signaling (CD3ζ, CD28, 4-1BB, and 2B4) leads to activation of PI3K or DNAX proteins (DAP10, DAP12) and finally to enhanced cytotoxicity, proliferation, and/or interferon γ release...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28649243/distinct-blood-and-visceral-adipose-tissue-regulatory-t-cell-and-innate-lymphocyte-profiles-characterize-obesity-and-colorectal-cancer
#4
Gloria Donninelli, Manuela Del Cornò, Marina Pierdominici, Beatrice Scazzocchio, Rosaria Varì, Barbara Varano, Ilenia Pacella, Silvia Piconese, Vincenzo Barnaba, Massimo D'Archivio, Roberta Masella, Lucia Conti, Sandra Gessani
Visceral adipose tissue (VAT) is a main site where metabolic and immunologic processes interplay to regulate, at local and systemic level, the inflammatory status and immune response. Obesity-associated inflammation and immune dysfunctions are inextricably linked to tumor but, in spite of intense efforts, the mechanisms underpinning this association remain elusive. In this report, we characterized the profile of VAT-associated and circulating innate lymphocyte and regulatory T (Treg) cell subsets underlying inflammatory conditions, such as obesity and colorectal cancer (CRC)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28648866/cytokines-in-immunogenic-cell-death-applications-for-cancer-immunotherapy
#5
REVIEW
Anne Showalter, Arati Limaye, Jeremiah L Oyer, Robert Igarashi, Christina Kittipatarin, Alicja J Copik, Annette R Khaled
Despite advances in treatments like chemotherapy and radiotherapy, metastatic cancer remains a leading cause of death for cancer patients. While many chemotherapeutic agents can efficiently eliminate cancer cells, long-term protection against cancer is not achieved and many patients experience cancer recurrence. Mobilizing and stimulating the immune system against tumor cells is one of the most effective ways to protect against cancers that recur and/or metastasize. Activated tumor specific cytotoxic T lymphocytes (CTLs) can seek out and destroy metastatic tumor cells and reduce tumor lesions...
June 22, 2017: Cytokine
https://www.readbyqxmd.com/read/28646364/sinonasal-malignancies-incidence-and-histological-distribution-in-jamaica-1973-2007
#6
Tracey N Gibson, Dawn P McNaughton, Barrie Hanchard
PURPOSE: To determine the histological distribution and trends in incidence of sinonasal malignancies in Jamaica. METHODS: Cases of all sinonasal malignancies diagnosed between 1973 and 2007 were extracted from the archives of the Jamaica Cancer Registry. Data recorded for each case included age at diagnosis, sex, year of diagnosis, topography, and histology. Data were used to calculate frequencies, age-specific incidence rates, and age-standardized incidence rates (ASRs)...
June 23, 2017: Cancer Causes & Control: CCC
https://www.readbyqxmd.com/read/28643847/ncr1-deficiency-diminishes-the-generation-of-protective-murine-cytomegalovirus-antibodies-by-limiting-follicular-helper-t-cell-maturation
#7
Antonija Miletic, Maja Lenartic, Branka Popovic, Ilija Brizic, Tihana Trsan, Karmela Miklic, Ofer Mandelboim, Astrid Krmpotic, Stipan Jonjic
NKp46/NCR1 is an activating NK-cell receptor implicated in the control of various viral and bacterial infections. Recent findings also suggest that it plays a role in shaping the adaptive immune response to pathogens. Using NCR1-deficient (NCR1(gfp/gfp) ) mice we provide evidence for the role of NCR1 in antibody response to mouse cytomegalovirus infection (MCMV). The absence of NCR1 resulted in impaired maturation, function and NK-cell migration to regional lymph nodes. In addition, CD4(+) T-cell activation and follicular helper T-cell (Tfh) generation were reduced, leading to inferior germinal center (GC) B-cell maturation...
June 23, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28642882/tumor-related-exosomes-contribute-to-tumor-promoting-microenvironment-an-immunological-perspective
#8
REVIEW
Wuzhen Chen, Jingxin Jiang, Wenjie Xia, Jian Huang
Exosomes are a kind of cell-released membrane-form structures which contain proteins, lipids, and nucleic acids. These vesicular organelles play a key role in intercellular communication. Numerous experiments demonstrated that tumor-related exosomes (TEXs) can induce immune surveillance in the microenvironment in vivo and in vitro. They can interfere with the maturation of DC cells, impair NK cell activation, induce myeloid-derived suppressor cells, and educate macrophages into protumor phenotype. They can also selectively induce effector T cell apoptosis via Fas/FasL interaction and enhance regulatory T cell proliferation and function by releasing TGF-β...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28642148/biological-activity-of-glatiramer-acetate-on-treg-and-anti-inflammatory-monocytes-persists-for-more-than-10years-in-responder-multiple-sclerosis-patients
#9
Michela Spadaro, Francesca Montarolo, Simona Perga, Serena Martire, Federica Brescia, Simona Malucchi, Antonio Bertolotto
Glatiramer acetate (GA) is a widely used treatment for multiple sclerosis (MS), with incompletely defined mechanism of action. Short-term studies suggested its involvement in the modulation of anti-inflammatory cytokines and regulatory T cells (Treg), while long-term effect is still unknown. To investigate this aspect, we analyzed by flow-cytometry peripheral-blood Treg, natural killer (NK), CD4 and CD8 T-cells and anti-inflammatory CD14(+)CD163(+) monocytes from 37 healthy donor and 90 RRMS patients divided in untreated, treated with GA for 12months and from 34 to 192months...
June 19, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28641638/-change-of-plasma-interleukin-17-level-in-patients-with-extranodal-nk-t-cell-lymphoma-and-its-clinical-significance
#10
Chun-Xiang Shang, Ji-Cheng Ma, Zheng Nan, Ye Li, Wen-Cai He, Xian-Ying Pan
OBJECTIVE: To investigate the clinical significance of interleukin-17 (IL-17) level in patients with extranodal NK/T-cell lymphoma(ENKTL). METHODS: Eighty patients with nasal ENKTL who received radiotherapy, chemotherapy or radiotherapy combined with chemotherapy from January 2011 to January 2012 were enrolled in the study. Eighty healthy volunteers were selected as the controls (control group). About 5 ml of peripheral blood was collected from all patients and controls...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28641636/-short-and-long-term-clinical-efficacy-of-imrt-and-crt-for-treatment-of-patients-with-enktl
#11
Jian-Xiong Cui, Wu-Hua Lin
OBJECTIVE: To compare the short and long term clinical efficacy for treatment of patients with extranodal nasal-type NK/T-cell lymphoma(ENKTL) by intensity modulated radiotherapy(IMRT) and conventional radiotheraphy(CRT). METHODS: Sixty-three cases of early ENKTL were divided into the IMRT group of (33 cases) and CRT group(30 cases). The short effects, overall survival(OS) of 3 years, progression free survival(PFS) of 3 years, acute radiation injury and late adverse reactions to radiation were compared between 2 group...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28639485/increased-shisa3-expression-characterizes-chronic-lymphocytic-leukemia-patients-sensitive-to-lenalidomide
#12
Rossana Maffei, Stefania Fiorcari, Silvia Martinelli, Stefania Benatti, Jenny Bulgarelli, Lara Rizzotto, Giulia Debbia, Rita Santachiara, Gian Matteo Rigolin, Francesco Forconi, Davide Rossi, Luca Laurenti, Giuseppe A Palumbo, Daniele Vallisa, Antonio Cuneo, Gianluca Gaidano, Mario Luppi, Roberto Marasca
Lenalidomide is a therapeutically effective drug in chronic lymphocytic leukemia (CLL). Twenty-seven CLL patients were treated with lenalidomide in a phase II clinical trial. Ten patients were grouped as responders (R) and 6 as nonresponders (NR). We evaluated T lymphocytes, NK, monocytes and dendritic cells at baseline and after treatment. A gene expression analysis was performed on 16 CLL samples collected before treatment. The levels of immune cells or immune-related cytokines are not different between R and NR patients...
June 22, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28638737/selective-activation-of-anti-cd73-mechanisms-in-control-of-primary-tumors-and-metastases
#13
Dipti Vijayan, Deborah S Barkauskas, Kimberley Stannard, Erin Sult, Rebecca Buonpane, Kazuyoshi Takeda, Michele W L Teng, Kris Sachsenmeier, Carl Hay, Mark J Smyth
The emerging role for CD73 in driving cancer growth and metastasis has presented opportunities to develop anti-CD73 monoclonal antibodies (mAbs) in the treatment of human cancers. Blockade of CD73 by antagonistic CD73 mAbs ameliorates tumor growth and metastasis via the inhibition of enzymatic and non-enzymatic CD73 pathways. In this study, we investigated whether Fc-receptor cross-linking represented a non-redundant mechanism by which anti-CD73 mAbs exert potent suppression of solid tumors and metastases. We engineered four anti-CD73 mAbs, each different in their ability to modulate CD73 enzymatic function and bind Fc receptors...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28638735/maternal-microchimerism-is-prevalent-in-cord-blood-in-memory-t-cells-and-other-cell-subsets-and-persists-post-transplant
#14
Sami B Kanaan, Hilary S Gammill, Whitney E Harrington, Stephen C De Rosa, Philip A Stevenson, Alexandra M Forsyth, Judy Allen, Emma Cousin, Koen van Besien, Colleen S Delaney, J Lee Nelson
Among reported advantages of umbilical cord blood (CB) in transplantation is lower leukemia relapse probability. Underlying cellular mechanisms of graft-vs.-leukemia (GVL) are thought to include a prominent role for T cells. Cells of the CB's mother, maternal microchimerism (MMc), were recently strongly, but indirectly, implicated in this GVL benefit. We assayed MMc directly and hypothesized benefit accrues from CB maternal T cells. MMc was quantified in 51 CBs and, within memory T, naïve T, B, NK cells, and monocytes in 27 CBs...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28638729/cellular-immunotherapies-for-cancer
#15
REVIEW
Pedro Berraondo, Sara Labiano, Luna Minute, Iñaki Etxeberria, Marcos Vasquez, Alvaro Sanchez-Arraez, Alvaro Teijeira, Ignacio Melero
Lessons learned over decades on the use of gene and cell therapies have found clinical applicability in the field of cancer immunotherapy. On December 16(th), 2016 a symposium was held in Pamplona (Spain) to analyze and discuss the critical points for the clinical success of adoptive cell transfer strategies in cancer immunotherapy. Cellular immunotherapy is being currently exploited for the development of new cancer vaccines using ex vivo manipulated dendritic cells or to enhance the number of effector cells, transferring reinvigorated NK cells or T cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28637895/cd4-cd8%C3%AE-double-positive-t-cells-in-skin-draining-lymph-nodes-respond-to-inflammatory-signals-from-the-skin
#16
Nana H Overgaard, Jazmina L Cruz, Jennifer A Bridge, Hendrik J Nel, Ian H Frazer, Nicole L La Gruta, Antje Blumenthal, Raymond J Steptoe, James W Wells
CD4(+)CD8(+) double-positive (DP), mature, peripheral T cells are readily detectable in a variety of species and tissues. Despite a common association with autoimmune and malignant skin disorders, however, little is understood about their role or function. Herein, we show that DP T cells are readily detectable in the blood, spleen, and peripheral lymph nodes of naïve C57BL/6 mice. DP T cells were also present in Jα18(-/-) and CD1d(-/-) mice, indicating that these cells are not NK-T cells. After skin administration of CASAC adjuvant, but not Quil A adjuvant, both total DP T cells and skin-infiltrating DP T cells increased in number...
June 21, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28637878/cd4-t-cell-and-nk-cell-interplay-key-to-regression-of-mhc-class-i-low-tumors-upon-tlr7-8-agonist-therapy
#17
Elien M Doorduijn, Marjolein Sluijter, Daniela C Salvatori, Serenella Silvestri, Saskia Maas, Ramon Arens, Ferry Ossendorp, Sjoerd H van der Burg, Thorbald van Hall
One of the next challenges in cancer immunotherapy is the resistance of tumors to T cell-based treatments through loss of MHC class I. Here, we show that under these circumstances, the Toll-like receptor (TLR)-7/8 ligand imiquimod, but not the TLR3 ligand poly I:C or TLR9 ligand CpG, mediated an effective antitumor response. The rejection of these immune-escaped cancers was mediated by NK cells and CD4(+) T cells, whereas activated CD8(+) T cells were dispensable. Application of the innate immune stimulator at a distant site activated NK cells and thereby elicited tumor-specific T-cell responses in tumor-bearing mice...
June 21, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28637877/ex-vivoexpanded-adaptive-nk-cells-effectively-kill-primary-acute-lymphoblastic-leukemia-cells
#18
Lisa L Liu, Vivien Beziat, Vincent Oei Yi Sheng, Aline Pfefferle, Marie Schaffer, Soren Lehmann, Eva Hellstrom-Lindberg, Stefan Soderhall, Mats Heyman, Dan Grander, Karl-Johan Malmberg
Manipulation of human NK cell repertoires promises more effective strategies for NK cell-based cancer immunotherapy. A subset of highly differentiated NK cells, termed adaptive NK cells, expands naturally in vivo in response to human cytomegalovirus (HCMV) infection, carries unique repertoires of inhibitory killer cell immunoglobulin-like receptors (KIRs), and displays strong cytotoxicity against tumor cells. Here, we established a robust and scalable protocol for ex vivo generation and expansion of adaptive NK cells for cell therapy against pediatric acute lymphoblastic leukemia (ALL)...
June 21, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28637584/decreased-tim-3-expression-of-peripheral-blood-natural-killer-cells-in-patients-with-severe-aplastic-anemia
#19
Tian Zhang, Xin Yuan, Chunyan Liu, Yi Li, Hui Liu, Lijuan Li, Kai Ding, Ting Wang, Honglei Wang, Zonghong Shao, Rong Fu
Severe aplastic anemia (SAA) is an autoimmune disease characterized by severe pancytopenia and bone marrow failure. In our previous studies, we found natural killer (NK) cells were aberrant in SAA patients. T cell immunoglobulin mucin-3 (TIM-3), an important regulator of immunity, is widely detected on NK cells and may contribute as a marker of activation and maturation of NK cells. In this study, we found that SAA untreated patients had lower TIM-3 expression on NK cells and CD56(dim) NK subsets compared with normal controls, and were correlated with the severity of pancytopenia of SAA...
April 24, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28637024/tumor-location-impacts-immune-response-in-mouse-models-of-colon-cancer
#20
Xianda Zhao, Lihua Li, Timothy K Starr, Subbaya Subramanian
Existing preclinical models of human colorectal cancer (CRC) that rely on syngeneic subcutaneous grafts are problematic, because of increasing evidence that the immune microenvironment in subcutaneous tissue is significantly different from the gastrointestinal tract. Similarly, existing orthotopic models that use a laparotomy for establishing grafts are also problematic, because the surgical procedure results in extensive inflammation, thereby creating a nonphysiologic tumor microenvironment. To facilitate the bench-to-bedside translation of CRC immunotherapy strategies, we developed a novel orthotopic model in mice that uses endoscopy-guided microinjection of syngeneic cancer cells...
June 9, 2017: Oncotarget
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