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Memory t cell cancer

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https://www.readbyqxmd.com/read/28817117/increased-tumor-infiltrating-cd45ra-ccr7-regulatory-t-cell-subset-with-immunosuppressive-properties-foster-gastric-cancer-progress
#1
Fang-Yuan Mao, Hui Kong, Yong-Liang Zhao, Liu-Sheng Peng, Weisan Chen, Jin-Yu Zhang, Ping Cheng, Ting-Ting Wang, Yi-Pin Lv, Yong-Sheng Teng, Xiao-Long Fu, Yu-Gang Liu, Xiao-Long Wu, Chuan-Jie Hao, Nan You, Ping Luo, Pei-Wu Yu, Quan-Ming Zou, Gang Guo, Yuan Zhuang
Regulatory T cells (Tregs) are major components of tumor-infiltrating immune cells with potent immunosuppressive properties in gastric cancer (GC) microenvironment. However, different subsets of the Tregs and their relevance to GC are unknown. Here, we found that patients with GC showed a significantly higher Tregs infiltration in tumors, and CD45RA(-)CCR7(-) Treg subset constituted most tumor-infiltrating Tregs. Tumor-infiltrating CD45RA(-)CCR7(-) Treg subset with an effector/memory phenotype accumulated in tumors and expressed low level of HLA-DR...
August 17, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28790368/signs-of-innate-immune-activation-and-premature-immunosenescence-in-psoriasis-patients
#2
Liisi Šahmatova, Elena Sügis, Marina Šunina, Helen Hermann, Ele Prans, Maire Pihlap, Kristi Abram, Ana Rebane, Hedi Peterson, Pärt Peterson, Külli Kingo, Kai Kisand
Psoriasis is a chronic inflammatory disease that affects skin and is associated with systemic inflammation and many serious comorbidities ranging from metabolic syndrome to cancer. Important discoveries about psoriasis pathogenesis have enabled the development of effective biological treatments blocking the T helper 17 pathway. However, it has not been settled whether psoriasis is a T cell-mediated autoimmune disease or an autoinflammatory disorder that is driven by exaggerated innate immune signalling. Our comparative gene expression and hierarchical cluster analysis reveal important gene circuits involving innate receptors...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28765518/characterization-of-infiltrating-lymphocytes-in-human-benign-and-malignant-prostate-tissue
#3
Emelie Rådestad, Lars Egevad, Carl Jorns, Jonas Mattsson, Berit Sundberg, Silvia Nava, Bo-Göran Ericzon, Lars Henningsohn, Victor Levitsky, Michael Uhlin
Immune checkpoint blockade has shown promising results in numerous cancer types. However, in prostate cancer (PC), absent or limited responses have been reported. To investigate further, we compared the phenotype of infiltrating T-cells isolated from prostate tissue from patients with PC (n = 5), benign prostatic hyperplasia (BPH) (n = 27), BPH with concurrent PC (n = 4) and controls (n = 7). The majority of T-cells were CD8+ and had a CCR7-CD45RO+ effector memory phenotype. However, the yield of T-cells isolated from PC lesions was on average 20-fold higher than that obtained from control prostates...
July 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28761757/mechanisms-of-action-and-rationale-for-the-use-of-checkpoint-inhibitors-in-cancer
#4
REVIEW
Clemence Granier, Eleonore De Guillebon, Charlotte Blanc, Helene Roussel, Cecile Badoual, Elia Colin, Antonin Saldmann, Alain Gey, Stephane Oudard, Eric Tartour
The large family of costimulatory molecules plays a crucial role in regulation of the immune response. These molecules modulate TCR signalling via phosphorylation cascades. Some of the coinhibitory members of this family, such as PD-1 and CTLA-4, already constitute approved targets in cancer therapy and, since 2011, have opened a new area of antitumour immunotherapy. Many antibodies targeting other inhibitory receptors (Tim-3, VISTA, Lag-3 and so on) or activating costimulatory molecules (OX40, GITR and so on) are under evaluation...
2017: ESMO Open
https://www.readbyqxmd.com/read/28759630/c77g-in-ptprc-cd45-is-no-risk-allele-for-ovarian-cancer-but-associated-with-less-aggressive-disease
#5
Johannes Landskron, Sigrid M Kraggerud, Elisabeth Wik, Anne Dørum, Merete Bjørnslett, Espen Melum, Øystein Helland, Line Bjørge, Ragnhild A Lothe, Helga B Salvesen, Kjetil Taskén
The pan lymphocyte marker CD45 exists in various isoforms arising from alternative splicing of the exons 4, 5 and 6. While naïve T cells express CD45RA translated from an mRNA containing exon 4, exons 4-6 are spliced out to encode the shorter CD45R0 in antigen-experienced effector/memory T cells. The SNP C77G (rs17612648) is located in exon 4 and blocks the exon's differential splicing from the pre-mRNA, enforcing expression of CD45RA. Several studies have linked C77G to autoimmune diseases but lack of validation in other cohorts has left its role elusive...
2017: PloS One
https://www.readbyqxmd.com/read/28755541/vaccines-targeting-helper-t-cells-for-cancer-immunotherapy
#6
REVIEW
Marit Melssen, Craig L Slingluff
There are compelling arguments for designing cancer vaccines specifically to induce CD4(+) helper T cell responses. Recent studies highlight the crucial role of proliferating, activated effector memory Th1 CD4(+) T cells in effective antitumor immunity and reveal that CD4(+) T cells induce more durable immune-mediated tumor control than CD8(+) T cells. CD4(+) T cells promote antitumor immunity by numerous mechanisms including enhancing antigen presentation, co-stimulation, T cell homing, T cell activation, and effector function...
July 26, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28751625/peripheral-cd4-na%C3%A3-ve-memory-ratio-is-an-independent-predictor-of-survival-in-non-small-cell-lung-cancer
#7
Peng Yang, Junhong Ma, Xin Yang, Wei Li
BACKGROUND: To investigate the clinical significance of naïve T cells, memory T cells, CD45RA+CD45RO+ T cells, and naïve/memory ratio in non-small cell lung cancer (NSCLC) patients. METHODS: Pretreatment peripheral blood samples from 76 NSCLC patients and 28 age- and sex-matched healthy volunteers were collected and tested for immune cells by flow cytometry. We compared the expression of these immune cells between patients and healthy controls and evaluated their predictive roles for survival in NSCLC by cox proportional hazards model...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28738020/resident-memory-t-cells-in-the-skin-mediate-durable-immunity-to-melanoma
#8
Brian T Malik, Katelyn T Byrne, Jennifer L Vella, Peisheng Zhang, Tamer B Shabaneh, Shannon M Steinberg, Aleksey K Molodtsov, Jacob S Bowers, Christina V Angeles, Chrystal M Paulos, Yina H Huang, Mary Jo Turk
Tissue-resident memory T (TRM) cells have been widely characterized in infectious disease settings; however, their role in mediating immunity to cancer remains unknown. We report that skin-resident memory T cell responses to melanoma are generated naturally as a result of autoimmune vitiligo. Melanoma antigen-specific TRM cells resided predominantly in melanocyte-depleted hair follicles and were maintained without recirculation or replenishment from the lymphoid compartment. These cells expressed CD103, CD69, and CLA (cutaneous lymphocyte antigen), but lacked PD-1 (programmed cell death protein-1) or LAG-3 (lymphocyte activation gene-3), and were capable of making IFN-γ (interferon-γ)...
April 14, 2017: Science Immunology
https://www.readbyqxmd.com/read/28733529/immunotherapy-of-wap-tnp-mice-with-early-stage-mammary-gland-tumors
#9
Michael Bruns, Wolfgang Deppert
The SV40 transgenic BALB/c mouse based WAP-T/WAP-TNP model for triple-negative breast cancer allows the analysis of parameters influencing immunotherapeutic approaches. Except for WAP-TNP tumors expressing the immune-dominant LCMV NP-epitope within SV40 T-antigen (T-AgNP) which is not expressed by T-Ag of WAP-T tumors, the tumors are extremely similar. Comparative anti-PD1/PD-L1 immunotherapy of WAP-T and WAP-TNP mice supported the hypothesis that the immunogenicity of tumor antigen T-cell epitopes strongly influences the success of immune checkpoint blockade therapy, with highly immunogenic T-cell epitopes favoring rapid CTL exhaustion...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723667/resistance-to-ctla-4-checkpoint-inhibition-reversed-through-selective-elimination-of-granulocytic-myeloid-cells
#10
Paul E Clavijo, Ellen C Moore, Jianhong Chen, Ruth J Davis, Jay Friedman, Young Kim, Carter Van Waes, Zhong Chen, Clint T Allen
PURPOSE: Local immunosuppression remains a critical problem that limits clinically meaningful response to checkpoint inhibition in patients with head and neck cancer. Here, we assessed the impact of MDSC elimination on responses to CTLA-4 checkpoint inhibition. EXPERIMENTAL DESIGN: Murine syngeneic carcinoma immune infiltrates were characterized by flow cytometry. Granulocytic MDSCs (gMDSCs) were depleted and T-lymphocyte antigen-specific responses were measured...
June 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28714866/ibrutinib-treatment-improves-t-cell-number-and-function-in-cll-patients
#11
Meixiao Long, Kyle Beckwith, Priscilla Do, Bethany L Mundy, Amber Gordon, Amy M Lehman, Kami J Maddocks, Carolyn Cheney, Jeffrey A Jones, Joseph M Flynn, Leslie A Andritsos, Farrukh Awan, Joseph A Fraietta, Carl H June, Marcela V Maus, Jennifer A Woyach, Michael A Caligiuri, Amy J Johnson, Natarajan Muthusamy, John C Byrd
BACKGROUND: Ibrutinib has been shown to have immunomodulatory effects by inhibiting Bruton's tyrosine kinase (BTK) and IL-2-inducible T cell kinase (ITK). The relative importance of inhibiting these 2 kinases has not been examined despite its relevance to immune-based therapies. METHODS: Peripheral blood mononuclear cells from chronic lymphocytic leukemia (CLL) patients on clinical trials of ibrutinib (BTK/ITK inhibitor; n = 19) or acalabrutinib (selective BTK inhibitor; n = 13) were collected serially...
August 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28707274/cancer-immunotherapies-are-they-as-effective-in-the-elderly
#12
Kate Poropatich, Joel Fontanarosa, Sandeep Samant, Jeffrey A Sosman, Bin Zhang
Almost two-thirds of all new cancer diagnoses are made in persons over the age of 65 years, yet it is unclear if age affects patient responsiveness to immunotherapy, which is increasingly becoming first-line therapy in advanced stages of different tumor types. Preclinical animal studies may be difficult to translate into humans since they frequently use young mice (2-3 months of age) equivalent to adolescent human subjects. Nevertheless, ex vivo studies from humans are concordant with mice tissue findings-older patients have an increased density of circulating regulatory immune cells and a decreased ratio of naïve-to-memory T cells...
August 2017: Drugs & Aging
https://www.readbyqxmd.com/read/28706974/sirolimus-increases-t-cell-abundance-in-the-sun-exposed-skin-of-kidney-transplant-recipients
#13
Michael Thomas Burke, Lauren C Sambira Nahum, Nicole M Isbel, Robert P Carroll, Hans Peter Soyer, Ross Francis, Jennifer Anne Bridge, Carmel Hawley, Kimberly Oliver, Christine E Staatz, James William Wells
BACKGROUND: Kidney transplant recipients (KTRs) receiving the mammalian target of rapamycin inhibitor sirolimus may display a reduced risk of skin cancer development compared to KTRs receiving calcineurin inhibitors. Despite studies investigating the effects of these 2 drug classes on T cells in patient blood, the effect these drugs may have in patient skin is not yet known. METHODS: Fifteen patients with chronic kidney disease (not recipients of immunosuppressive drugs), and 30 KTRs (15 receiving a calcineurin inhibitor, and 15 receiving sirolimus) provided matched samples of blood, sun exposed (SE) and non-SE skin...
July 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28692671/immune-profiles-and-clinical-outcomes-between-sepsis-patients-with-or-without-active-cancer-requiring-admission-to-intensive-care-units
#14
Wen-Feng Fang, Yu-Mu Chen, Chiung-Yu Lin, Kuo-Tung Huang, Hsu-Ching Kao, Ying-Tang Fang, Chi-Han Huang, Ya-Ting Chang, Yi-His Wang, Chin-Chou Wang, Meng-Chih Lin
BACKGROUND: Immunoparalysis was observed in both patients with cancer and sepsis. In cancer patients, Cytotoxic T lymphocyte antigen-4 and programmed cell death protein 1/programmed death-ligand 1 axis are two key components of immunoparalysis. Several emerging therapies against these two axes gained significant clinical benefit. In severe sepsis patients, immunoparalysis was known as compensatory anti-inflammatory response syndrome and this has been suggested as an important cause of death in patients with sepsis...
2017: PloS One
https://www.readbyqxmd.com/read/28685239/a-biodesign-approach-to-obtain-high-yields-of-biosimilars-by-anti-apoptotic-cell-engineering-a-case-study-to-increase-the-production-yield-of-anti-tnf-alpha-producing-recombinant-cho-cells
#15
Sultan Gulce Iz, Muge Anil Inevi, Pelin Saglam Metiner, Duygu Ayyildiz Tamis, Nazli Kisbet
Recent developments in medical biotechnology have facilitated to enhance the production of monoclonal antibodies (mAbs) and recombinant proteins in mammalian cells. Human mAbs for clinical applications have focused on three areas, particularly cancer, immunological disorders, and infectious diseases. Tumor necrosis factor alpha (TNF-α), which has both proinflammatory and immunoregulatory functions, is an important target in biopharmaceutical industry. In this study, a humanized anti-TNF-α mAb producing stable CHO cell line which produces a biosimilar of Humira (adalimumab) was used...
July 6, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/28684164/neem-leaf-glycoprotein-generates-superior-tumor-specific-central-memory-cd8-t-cells-than-cyclophosphamide-that-averts-post-surgery-solid-sarcoma-recurrence
#16
Sarbari Ghosh, Madhurima Sarkar, Tithi Ghosh, Ipsita Guha, Avishek Bhuniya, Akata Saha, Shayani Dasgupta, Subhasis Barik, Anamika Bose, Rathindranath Baral
The success of cancer vaccines is limited as most of them induce corrupted CD8(+) T cell memory populations. We reported earlier that a natural immunomodulator, neem leaf glycoprotein (NLGP), therapeutically restricts tumor growth in a CD8(+) T cell-dependent manner. Here, our objective is to study whether memory CD8(+) T cell population is generated in sarcoma hosts after therapeutic NLGP treatment and their role in prevention of post-surgery tumor recurrence, in comparison to the immunostimulatory metronomic cyclophosphamide (CTX) treatment...
July 3, 2017: Vaccine
https://www.readbyqxmd.com/read/28679778/combination-therapy-with-nhs-muil12-and-avelumab-anti-pd-l1-enhances-antitumor-efficacy-in-preclinical-cancer-models
#17
Chunxiao Xu, Yanping Zhang, P Alexander Rolfe, Vivian M Hernández, Wilson Guzman, Giorgio Kradjian, Bo Marelli, Guozhong Qin, Jin Qi, Hong Wang, Huakui Yu, Robert Tighe, Kin-Ming Lo, Jessie M English, Laszlo G Radvanyi, Yan Lan
To determine if combination therapy with NHS-muIL12 and the anti-PD-L1 antibody avelumab can enhance anti-tumor efficacy in preclinical models relative to monotherapies.<br /><br />Experimental Design: BALB/c mice bearing orthotopic EMT-6 mammary tumors and μMt(-) mice bearing subcutaneous MC38 tumors were treated with NHS-muIL12, avelumab, or combination therapy; tumor growth and survival were assessed. Tumor recurrence following remission and rechallenge was evaluated in EMT-6 tumor-bearing mice...
July 5, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28679768/pd-1-%C3%A2-polyfunctional-t-cells-dominate-the-periphery-after-tumor-infiltrating-lymphocyte-therapy-for-cancer
#18
Marco Donia, Julie Westerlin Kjeldsen, Rikke Andersen, Marie Christine Wulff Westergaard, Valentina Bianchi, Mateusz Legut, Meriem Attaf, Barbara Szomolay, Sascha Ott, Garry Dolton, Rikke Lyngaa, Sine Reker Hadrup, Andrew K Sewell, Inge Marie Svane
Infusion of highly heterogeneous populations of autologous tumor-infiltrating lymphocytes (TILs) can result in tumor regression of exceptional duration. Initial tumor regression has been associated with persistence of tumor-specific TILs one month after infusion, but mechanisms leading to long-lived memory responses are currently unknown. Here we studied the dynamics of bulk tumor-reactive CD8(+) T cell populations in patients with metastatic melanoma following treatment with TILs. <p>Experimental Design: We analyzed the function and phenotype of tumor-reactive CD8(+) T cells contained in serial blood samples of sixteen patients treated with TILs</p> <p>Results: Polyfunctional tumor-reactive CD8(+) T cells accumulated over time in the peripheral lymphocyte pool...
July 5, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28679475/cik-as-therapeutic-agents-against-tumors
#19
REVIEW
M Introna
Cytokine Induced Killer (CIK) cells are ex vivo expanded and activated T lymphocytes obtained by sequential incubation of Peripheral Blood Mononuclear cells (PBMNC) with Interferon γ (IFNG), anti CD3 monoclonal antibody OKT3 and IL2. These cells, while retaining few characteristics of the Effector memory T cells subpopulation, acquired during culture CD56 expression, as well as non specific, Natural Killer like, anti tumoral cytotoxicity. CIK cells from human are equivalent to expanded NKT cells in mouse...
July 2, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28674001/delineation-of-an-immunosuppressive-gradient-in-hepatocellular-carcinoma-using-high-dimensional-proteomic-and-transcriptomic-analyses
#20
Valerie Chew, Liyun Lai, Lu Pan, Chun Jye Lim, Juntao Li, Raymond Ong, Camillus Chua, Jing Yao Leong, Kiat Hon Lim, Han Chong Toh, Ser Yee Lee, Chung Yip Chan, Brian K P Goh, Alexander Chung, Pierce K H Chow, Salvatore Albani
The recent development of immunotherapy as a cancer treatment has proved effective over recent years, but the precise dynamics between the tumor microenvironment (TME), nontumor microenvironment (NTME), and the systemic immune system remain elusive. Here, we interrogated these compartments in hepatocellular carcinoma (HCC) using high-dimensional proteomic and transcriptomic analyses. By time-of-flight mass cytometry, we found that the TME was enriched in regulatory T cells (Tregs), tissue resident memory CD8(+) T cells (TRMs), resident natural killer cells (NKRs), and tumor-associated macrophages (TAMs)...
July 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
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