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https://www.readbyqxmd.com/read/28971402/-mir-140-3p-downregulation-in-association-with-pdl-1-overexpression-in-many-cancers-a-review-from-the-literature-using-predictive-bioinformatics-tools
#1
Nikolaos Kapodistrias, Catherine Bobori, Georgia Theocharopoulou
Programmed death-ligand 1 (PD-L1) has been speculated to play a critical role in suppression of the immune system and it can be upregulated in cancer cells, which may allow cancers to evade the host immune system. MicroRNAs (miRNAs) are small non-coding RNA molecules (containing about 22 nucleotides), that function in RNA silencing and post-transcriptional regulation of gene expression. MiRNAs were found deregulated (upregulated or downregulated) and implicated in cancer development with various roles which depend on their gene target...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28932633/cd163-positive-tumor-associated-macrophages-and-cd8-positive-cytotoxic-lymphocytes-are-powerful-diagnostic-markers-for-the-therapeutic-stratification-of-osteosarcoma-patients-an-immunohistochemical-analysis-of-the-biopsies-fromthe-french-os2006-phase-3-trial
#2
Anne Gomez-Brouchet, Claire Illac, Julia Gilhodes, Corinne Bouvier, Sébastien Aubert, Jean-Marc Guinebretiere, Béatrice Marie, Frédérique Larousserie, Natacha Entz-Werlé, Gonzague de Pinieux, Thomas Filleron, Véronique Minard, Vincent Minville, Eric Mascard, François Gouin, Marta Jimenez, Marie-Cécile Ledeley, Sophie Piperno-Neumann, Laurence Brugieres, Françoise Rédini
The French phase 3 trial (OS 2006) testing zoledronic acid, an osteoclast inhibitor, with chemotherapy and surgery did not improve the outcome of patients with osteosarcoma (OS). To understand this unexpected result, the presence of infiltrating immune cells was investigated in 124 pre-therapeutic biopsies of patients enrolled in the trial. The percentage of CD68/CD163 tumor-infiltrating macrophages (TAMs), CD8(+) lymphocytes, osteoclasts, and the PD1/PDL-1 checkpoint were assessed by immunohistochemistry. M1/M2 macrophage polarization was characterized by pSTAT1/CMAF staining...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28878676/pd-1-and-pd-l1-checkpoint-signaling-inhibition-for-cancer-immunotherapy-mechanism-combinations-and-clinical-outcome
#3
REVIEW
Hashem O Alsaab, Samaresh Sau, Rami Alzhrani, Katyayani Tatiparti, Ketki Bhise, Sushil K Kashaw, Arun K Iyer
Several cancers are highly refractory to conventional chemotherapy. The survival of tumors in several cases is assisted by checkpoint immunomodulation to maintain the imbalance between immune surveillance and cancer cell proliferation. Check point antibody inhibitors, such as anti-PD-1/PD-L1, are a novel class of inhibitors that function as a tumor suppressing factor via modulation of immune cell-tumor cell interaction. These checkpoint blockers are rapidly becoming a highly promising cancer therapeutic approach that yields remarkable antitumor responses with limited side effects...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28869918/circulating-cd4-pd-1-and-cd8-pd-1-t-cells-are-profoundly-decreased-at-the-onset-of-fulminant-type-1-diabetes-and-are-restored-by-treatment-contrasting-with-cd4-cd25-foxp3-regulatory-t-cells
#4
Toshie Iijima, Kanako Kato, Teruo Jojima, Takanori Tomotsune, Maiko Fukushima, Kunihiro Suzuki, Yoshimasa Aso
Programed cell death protein-1 (PD-1) is an inhibitory receptor expressed by T cells that downregulates the activation and proliferation of these cells to maintain peripheral self-tolerance. Recent studies reported some cases of new-onset type 1 diabetes (T1D) under anti-PD1 or PDL-1 antibodies. We demonstrated that circulating both CD4+PD-1+ and CD8+PD-1+ T cells were profoundly reduced at the onset of fulminant T1D and were restored by treatment in two patients with fulminant T1D.
July 31, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28855904/immunological-properties-of-murine-parthenogenetic-stem-cell-derived-cardiomyocytes-and-engineered-heart-muscle
#5
Michael Didié, Satish Galla, Vijayakumar Muppala, Ralf Dressel, Wolfram-Hubertus Zimmermann
Pluripotent parthenogenetic stem cells (pSCs) can be derived by pharmacological activation of unfertilized oocytes. Homozygosity of the major histocompatibility complex (MHC) in pSCs makes them an attractive cell source for applications in allogeneic tissue repair. This was recently demonstrated for pSC-based tissue-engineered heart repair. A detailed analysis of immunological properties of pSC-derived cardiomyocytes and engineered heart muscle (EHM) thereof is, however, lacking. The aim of this study was to determine baseline and cytokine-inducible MHC class I and MHC class II as well as programmed death ligand-1 (PDL-1) and co-stimulatory protein (CD40, CD80, CD86) expression in pSC-derived cardiomyocytes and pSC-EHM in vitro and in vivo...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28831825/pdl-1-pd1-inhibitors-antibody-or-antinobody
#6
Fouad Aoun, Elie El Rassy, Tarek Assi, Joseph Kattan
No abstract text is available yet for this article.
August 2017: Future Oncology
https://www.readbyqxmd.com/read/28815334/clinical-characteristics-of-patient-selection-and-imaging-predictors-of-outcome-in-solid-tumors-treated-with-checkpoint-inhibitors
#7
REVIEW
Sabrina Rossi, Luca Toschi, Angelo Castello, Fabio Grizzi, Luigi Mansi, Egesta Lopci
The rapidly evolving knowledge on tumor immunology and the continuous implementation of immunotherapy in cancer have recently led to the FDA and EMA approval of several checkpoint inhibitors as immunotherapic agents in clinical practice. Anti-CTLA-4, anti-PD-1, and anti-PDL-1 antibodies are becoming standard of care in advanced melanoma, as well as in relapsed or metastatic lung and kidney cancer, demonstrating higher and longer response compared to standard chemotherapy. These encouraging results have fostered the evaluation of these antibodies either alone or in combination with other therapies in several dozen clinical trials for the treatment of multiple tumor types...
August 16, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28673339/human-limbal-fibroblast-like-stem-cells-induce-immune-tolerance-in-autoreactive-t-lymphocytes-from-female-patients-with-hashimoto-s-thyroiditis
#8
Antonina Coppola, Laura Tomasello, Maria Pitrone, Salvatore Cillino, Pierina Richiusa, Giuseppe Pizzolanti, Carla Giordano
BACKGROUND: Due to their "natural immune privilege" and immunoregulatory properties human fibroblast-like limbal stem cells (f-LSCs) have acquired great interest as a potential tool for achieving immunotolerance. Hashimoto's thyroiditis (HT) is the most common thyroid autoimmune disease and cause of hypothyroidism. To date, conventional hormone replacement therapy and unspecific immunosuppressive regimens cannot provide a definitive cure for HT subjects. We explored the immunosuppressant potential of human f-LSCs on circulating lymphomonocytes (PBMCs) collected from healthy donors and female HT patients...
July 3, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28671973/pd-l1-expression-in-pleomorphic-spindle-cell-and-giant-cell-carcinoma-of-the-lung-is-related-to-ttf-1-p40-expression-and-might-indicate-a-worse-prognosis
#9
Violaine Yvorel, Arnaud Patoir, François Casteillo, Claire Tissot, Pierre Fournel, Marie-Laure Stachowicz, Georgia Karpathiou, Olivier Tiffet, Michel Péoc'h, Fabien Forest
Lung sarcomatoid carcinoma of the lung is a rare tumor with a poor prognosis. More than 90% of them are pleomorphic, spindle cell and giant cell carcinoma (PSCGCC). This rare subtype of lung cancer is thought to be more resistant to chemotherapy, and a small subset of them seems to exhibit targetable mutations. Immunotherapy against PD1/PDL-1 is a new emerging treatment, and might be of interest in PSGSCC because they frequently express PD-L1. The aim of our work is to evaluate PD1 and PDL-1 expression in a surgical series of lung PSCGCC and their relationship with morphological and immunohistochemical parameters and prognosis...
2017: PloS One
https://www.readbyqxmd.com/read/28631301/prevention-of-lupus-nephritis-development-in-nzb-nzw-mice-by-selective-blockade-of-cd28
#10
Laetitia Laurent, Awena Le Fur, Rozenn Le Bloas, Mélanie Néel, Caroline Mary, Anne Moreau, Nicolas Poirier, Bernard Vanhove, Fadi Fakhouri
Systemic lupus erythematosus (SLE) is a chronic systemic inflammatory disease. Autoantibodies (autoAbs) against double-stranded DNA (ds DNA), the hallmark of lupus, are produced and maintained by the interaction between auto-reactive B cells and CD4(+) T cells. This interplay is controlled by the CD28/CD80-86/CTLA-4 axis. Here we investigated whether selective blockade of CD28-CD80/86 co-stimulatory interactions abrogates lupus nephritis development in a murine model of SLE. To this aim, NZB/NZW F1 mice were treated for 3 months, either with an anti-CD28 Fab' fragment or a control Fab'-IgG...
August 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28542267/discerning-morpho-anatomical-physiological-and-molecular-multiformity-in-cultivated-and-wild-genotypes-of-lentil-with-reconciliation-to-salinity-stress
#11
Dharmendra Singh, Chandan Kumar Singh, Shanti Kumari, Ram Sewak Singh Tomar, Sourabh Karwa, Rajendra Singh, Raja Bahadur Singh, Susheel Kumar Sarkar, Madan Pal
One hundred and sixty two genotypes of different Lens species were screened for salinity tolerance in hydroponics at 40, 80 and 120 mM sodium chloride (NaCl) for 30 d. The germination, seedling growth, biomass accumulation, seedling survivability, salinity scores, root and shoot anatomy, sodium ion (Na+), chloride ion (Cl-) and potassium ion (K+) concentrations, proline and antioxidant activities were measured to evaluate the performance of all the genotypes. The results were compared in respect of physiological (Na+, K+ and Cl-) and seed yield components obtained from field trials for salinity stress conducted during two years...
2017: PloS One
https://www.readbyqxmd.com/read/28522749/expansion-of-tumor-infiltrating-cd8-t-cells-expressing-pd-1-improves-the-efficacy-of-adoptive-t-cell-therapy
#12
Sarita M Fernandez-Poma, Diego Salas-Benito, Teresa Lozano, Noelia Casares, Jose-Ignacio Riezu-Boj, Uxua Mancheño, Edurne Elizalde, Diego Alignani, Natalia Zubeldia, Itziar Otano, Enrique Conde, Pablo Sarobe, Juan Jose Lasarte, Sandra Hervas-Stubbs
Recent studies have found that tumor-infiltrating lymphocytes (TIL) expressing PD-1 can recognize autologous tumor cells, suggesting that cells derived from PD-1(+) TILs can be used in adoptive T-cell therapy (ACT). However, no study thus far has evaluated the antitumor activity of PD-1-selected TILs in vivo In two mouse models of solid tumors, we show that PD-1 allows identification and isolation of tumor-specific TILs without previous knowledge of their antigen specificities. Importantly, despite the high proportion of tumor-reactive T cells present in bulk CD8 TILs before expansion, only T-cell products derived from sorted PD-1(+), but not from PD-1(-) or bulk CD8 TILs, specifically recognized tumor cells...
July 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28488345/patterns-of-pd-1-pd-l1-and-pd-l2-expression-in-pediatric-solid-tumors
#13
Navin Pinto, Julie R Park, Erin Murphy, Jennifer Yearley, Terri McClanahan, Lakshmanan Annamalai, Douglas S Hawkins, Erin R Rudzinski
BACKGROUND: Significant antitumor effects have been observed in a variety of malignancies via blockade of immune checkpoints. Interaction of programmed death 1 (PD-1) with its ligands PD-L1 and PD-L2 suppresses T-cell function and restricts immune-mediated tumor killing. We examined expression of these proteins in children with solid tumors, as expression may serve as biomarkers of response to this class of drugs. METHODS: Sections cut from formalin-fixed paraffin-embedded (FFPE) tissue blocks were processed and evaluated for PD-1, PD-L1, and PD-L2 by immunohistochemistry (IHC) as well as by mRNA expression...
November 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28476944/impact-of-age-on-outcomes-with-immunotherapy-for-patients-with-melanoma
#14
Allison S Betof, Ryan D Nipp, Anita Giobbie-Hurder, Romany A N Johnpulle, Krista Rubin, Samuel M Rubinstein, Keith T Flaherty, Donald P Lawrence, Douglas B Johnson, Ryan J Sullivan
BACKGROUND: Monoclonal antibodies (mAb) targeting PD-1/PD-L1 have revolutionized melanoma treatment, yet data regarding effectiveness and tolerability across age groups is limited. We sought to determine the impact of age on overall survival (OS), progression-free survival (PFS), and rates of immune-mediated toxicities in patients treated with anti-PD-1/anti-PD-L1 mAb at two academic medical centers. METHODS: We retrospectively collected data on all patients with metastatic melanoma treated with anti-PD-1/PD-L1 mAb between May 2009 and April 2015...
August 2017: Oncologist
https://www.readbyqxmd.com/read/28403039/pneumotoxicity-associated-with-immune-checkpoint-inhibitor-therapies
#15
Vickie R Shannon
PURPOSE OF REVIEW: Immune checkpoint inhibitor therapies represent a new paradigm in cancer therapeutics, in which the targets are not the cancer cells, but the body's own immune system. Harnessing the immune system to better fight cancer has generated a unique spectrum of immune-related adverse events (IrAEs) that effect virtually every major organ system. Although lung involvement is less common than other forms of IrAEs, its consequences are potentially lethal. This review focuses on the evolving spectrum of lung toxicities associated with the two major classes of immune checkpoint inhibitor therapies, cytotoxic T-cell ligand-4, and programed cell death-1 (PDL-1)...
July 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/28391420/a-neuro-oncologist-s-perspective-on-management-of-brain-metastases-in-patients-with-egfr-mutant-non-small-cell-lung-cancer
#16
REVIEW
Tresa McGranahan, Seema Nagpal
Management of non-small cell lung cancer (NSCLC) with brain metastasis (BrM) has been revolutionized by identification of molecular subsets that have targetable oncogenes. Historically, survival for NSCLC with symptomatic BrM was weeks to months. Now, many patients are surviving years with limited data to guide treatment decisions. Tumors with activating mutations in epidermal growth factor receptor (EGFRact+) have a higher incidence of BrM, but a longer overall survival. The high response rate of both systemic and BrM EGFRact+ NSCLC to tyrosine kinase inhibitors (TKIs) has led to the rapid incorporation of new therapies but is outpacing evidence-based decisions for BrM in NSCLC...
April 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28357911/advances-in-urothelial-bladder-cancer-immunotherapy-dawn-of-a-new-age-of-treatment
#17
REVIEW
Fouad Aoun, Elie El Rassy, Tarek Assi, Simone Albisinni, Joseph Katan
Urothelial bladder cancer displays a high number of somatic mutations that render these tumors more responsive to immunotherapy. Several immunotherapeutic agents were examined in patients with advanced stage urothelial bladder cancer and recently atezolizumab - an (PDL-1) immune checkpoint inhibitor antibody - was approved for the treatment of patients with metastatic disease progressing after platinum combination therapy. Despite the great success, there are still some unanswered questions and ongoing trials that are in progress to define the role of combination therapy and sequencing strategies...
March 2017: Immunotherapy
https://www.readbyqxmd.com/read/28345023/enhancement-of-psma-directed-car-adoptive-immunotherapy-by-pd-1-pd-l1-blockade
#18
Inna Serganova, Ekaterina Moroz, Ivan Cohen, Maxim Moroz, Mayuresh Mane, Juan Zurita, Larissa Shenker, Vladimir Ponomarev, Ronald Blasberg
Chimeric antigen receptor (CAR) T cell therapy in hematologic malignancies has shown remarkable responses, but the same level of success has not been observed in solid tumors. A new prostate cancer model (Myc-CaP:PSMA(+)) and a second-generation anti-hPSMA human CAR T cells expressing a Click Beetle Red luciferase reporter) were used to study hPSMA targeting and assess CAR T cell trafficking and persistence by bioluminescence imaging (BLI). We investigated the antitumor efficacy of human CAR T cells targeting human prostate-specific membrane antigen (hPSMA), in the presence and absence of the target antigen; first alone and then combined with a monoclonal antibody targeting the human programmed death receptor 1 (anti-hPD1 mAb)...
March 17, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28318336/are-tumor-infiltrating-lymphocytes-protagonists-or-background-actors-in-patient-selection-for-cancer-immunotherapy
#19
Federica Zito Marino, Paolo Antonio Ascierto, Giulio Rossi, Stefania Staibano, Marco Montella, Daniela Russo, Roberto Alfano, Alessandro Morabito, Gerardo Botti, Renato Franco
Tumor-infiltrating lymphocytes (TILs) are frequently observed in several tumors, reflecting the dynamic process of '"cancer immunoediting"'. Prognostic and predictive values of TILs have been demonstrated in different cancers, proving their pivotal role in clinical outcome. In recent years, new therapies targeting immune checkpoint inhibitors, especially CTLA-4 and PD-1/PDL-1 pathways, have been introduced into clinical practice. In this context, TILs may even have a possible utility as a predictive biomarker for immunotherapy response...
June 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28230773/programmed-death-ligand-1-pd-l1-tumor-expression-is-associated-with-a-better-prognosis-and-diabetic-disease-in-triple-negative-breast-cancer-patients
#20
Gerardo Botti, Francesca Collina, Giosuè Scognamiglio, Federica Rao, Valentina Peluso, Rossella De Cecio, Michela Piezzo, Gabriella Landi, Michelino De Laurentiis, Monica Cantile, Maurizio Di Bonito
Triple Negative Breast Cancers (TNBC) subtype is an aggressive disease with poor clinical outcome. The only treatment available is surgery followed by chemotherapy or radiotherapy. Programmed death-ligand 1 (PD-L1) is a trans-membrane protein expressed on a wide variety of cells including immune cells, epithelial and vascular endothelial cells. Recently, PD-1/PD-L1 pathway signaling was described as an adaptive immune resistance mechanism enacted by the tumor cells to evade the immune response. Its presence on tumor cell membranes, acquired for this reason, through time, is an important prognostic value...
February 21, 2017: International Journal of Molecular Sciences
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