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https://www.readbyqxmd.com/read/28350989/mir-219-cooperates-with-mir-338-in-myelination-and-promotes-myelin-repair-in-the-cns
#1
Haibo Wang, Ana Lis Moyano, Zhangyan Ma, Yaqi Deng, Yifeng Lin, Chuntao Zhao, Liguo Zhang, Minqing Jiang, Xuelian He, Zhixing Ma, Fanghui Lu, Mei Xin, Wenhao Zhou, Sung Ok Yoon, Ernesto R Bongarzone, Q Richard Lu
A lack of sufficient oligodendrocyte myelination contributes to remyelination failure in demyelinating disorders. miRNAs have been implicated in oligodendrogenesis; however, their functions in myelin regeneration remained elusive. Through developmentally regulated targeted mutagenesis, we demonstrate that miR-219 alleles are critical for CNS myelination and remyelination after injury. Further deletion of miR-338 exacerbates the miR-219 mutant hypomyelination phenotype. Conversely, miR-219 overexpression promotes precocious oligodendrocyte maturation and regeneration processes in transgenic mice...
March 27, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28346697/car-t-cell-therapy-for-pancreatic-cancer
#2
REVIEW
Carl J DeSelm, Zachary E Tano, Anna M Varghese, Prasad S Adusumilli
Chimeric antigen receptor (CAR) T-cell therapy utilizes genetic engineering to redirect a patient's own T cells to target cancer cells. The remarkable results in hematological malignancies prompted investigating this approach in solid tumors such as pancreatic cancer. The complex tumor microenvironment, stromal hindrance in limiting immune response, and expression of checkpoint blockade on T cells pose hurdles. Herein, we summarize the opportunities, challenges, and state of knowledge in targeting pancreatic cancer with CAR T-cell therapy...
March 27, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28346412/vista-is-an-inhibitory-immune-checkpoint-that-is-increased-after-ipilimumab-therapy-in-patients-with-prostate-cancer
#3
Jianjun Gao, John F Ward, Curtis A Pettaway, Lewis Z Shi, Sumit K Subudhi, Luis M Vence, Hao Zhao, Jianfeng Chen, Hong Chen, Eleni Efstathiou, Patricia Troncoso, James P Allison, Christopher J Logothetis, Ignacio I Wistuba, Manuel A Sepulveda, Jingjing Sun, Jennifer Wargo, Jorge Blando, Padmanee Sharma
To date, anti-CTLA-4 (ipilimumab) or anti-PD-1 (nivolumab) monotherapy has not been demonstrated to be of substantial clinical benefit in patients with prostate cancer. To identify additional immune-inhibitory pathways in the prostate-tumor microenvironment, we evaluated untreated and ipilimumab-treated tumors from patients in a presurgical clinical trial. Levels of the PD-L1 and VISTA inhibitory molecules increased on independent subsets of macrophages in treated tumors. Our data suggest that VISTA represents another compensatory inhibitory pathway in prostate tumors after ipilimumab therapy...
March 27, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28346400/t-lymphocyte-homing-an-underappreciated-yet-critical-hurdle-for-successful-cancer-immunotherapy
#4
Robert Sackstein, Tobias Schatton, Steven R Barthel
Advances in cancer immunotherapy have offered new hope for patients with metastatic disease. This unfolding success story has been exemplified by a growing arsenal of novel immunotherapeutics, including blocking antibodies targeting immune checkpoint pathways, cancer vaccines, and adoptive cell therapy (ACT). Nonetheless, clinical benefit remains highly variable and patient-specific, in part, because all immunotherapeutic regimens vitally hinge on the capacity of endogenous and/or adoptively transferred T-effector (Teff) cells, including chimeric antigen receptor (CAR) T cells, to home efficiently into tumor target tissue...
March 27, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28346230/glutaminase-and-poly-adp-ribose-polymerase-inhibitors-suppress-pyrimidine-synthesis-and-vhl-deficient-renal-cancers
#5
Arimichi Okazaki, Paulo A Gameiro, Danos Christodoulou, Laura Laviollette, Meike Schneider, Frances Chaves, Anat Stemmer-Rachamimov, Stephanie A Yazinski, Richard Lee, Gregory Stephanopoulos, Lee Zou, Othon Iliopoulos
Many cancer-associated mutations that deregulate cellular metabolic responses to hypoxia also reprogram carbon metabolism to promote utilization of glutamine. In renal cell carcinoma (RCC), cells deficient in the von Hippel-Lindau (VHL) tumor suppressor gene use glutamine to generate citrate and lipids through reductive carboxylation (RC) of α-ketoglutarate (αKG). Glutamine can also generate aspartate, the carbon source for pyrimidine biosynthesis, and glutathione for redox balance. Here we have shown that VHL-/- RCC cells rely on RC-derived aspartate to maintain de novo pyrimidine biosynthesis...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28346226/a-tlr9-dependent-checkpoint-governs-b-cell-responses-to-dna-containing-antigens
#6
Vishal J Sindhava, Michael A Oropallo, Krishna Moody, Martin Naradikian, Lauren E Higdon, Lin Zhou, Arpita Myles, Nathaniel Green, Kerstin Nündel, William Stohl, Amanda M Schmidt, Wei Cao, Stephanie Dorta-Estremera, Taku Kambayashi, Ann Marshak-Rothstein, Michael P Cancro
Mature B cell pools retain a substantial proportion of polyreactive and self-reactive clonotypes, suggesting that activation checkpoints exist to reduce the initiation of autoreactive B cell responses. Here, we have described a relationship among the B cell receptor (BCR), TLR9, and cytokine signals that regulate B cell responses to DNA-containing antigens. In both mouse and human B cells, BCR ligands that deliver a TLR9 agonist induce an initial proliferative burst that is followed by apoptotic death. The latter mechanism involves p38-dependent G1 cell-cycle arrest and subsequent intrinsic mitochondrial apoptosis and is shared by all preimmune murine B cell subsets and CD27- human B cells...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28345633/t-cells-successful-checkpoint-blockade-requires-positive-co-stimulation
#7
Alexandra Flemming
No abstract text is available yet for this article.
March 27, 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28344892/clear-cell-ovarian-cancers-with-microsatellite-instability-a-unique-subset-of-ovarian-cancers-with-increased-tumor-infiltrating-lymphocytes-and-pd-1-pd-l1-expression
#8
Brooke E Howitt, Kyle C Strickland, Lynette M Sholl, Scott Rodig, Lauren L Ritterhouse, Dipanjan Chowdhury, Alan D D'Andrea, Ursula A Matulonis, Panagiotis A Konstantinopoulos
Clear cell ovarian carcinoma (CCOC) represents a distinct histologic subtype of ovarian cancer associated with significantly worse prognosis across all stages and no effective therapeutic options. Here, we report a rare but clinically important cohort of CCOCs with microsatellite instability (MSI) (MSI-CCOCs), which are highly immunogenic and may thus be very responsive to immune checkpoint blockade. CCOCs with MSI exhibit a significantly higher number of CD8(+) TILs, higher CD8(+)/CD4(+) ratio, and higher PD-1(+) TILs compared with microsatellite stable (MSS) CCOCs and compared with high grade serous ovarian cancers, which are the most common histologic subtype of ovarian cancer...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344890/suppression-of-indoleamine-2-3-dioxygenase-1-expression-by-promoter-hypermethylation-in-er-positive-breast-cancer
#9
Dyah L Dewi, Soumya R Mohapatra, Saioa Blanco Cabañes, Isabell Adam, Luis F Somarribas Patterson, Bianca Berdel, Masroor Kahloon, Loreen Thürmann, Stefanie Loth, Katharina Heilmann, Dieter Weichenhan, Oliver Mücke, Ines Heiland, Pauline Wimberger, Jan Dominik Kuhlmann, Karl-Heinz Kellner, Sarah Schott, Christoph Plass, Michael Platten, Clarissa Gerhäuser, Saskia Trump, Christiane A Opitz
Kynurenine formation by tryptophan-catabolic indoleamine-2,3-dioxygenase 1 (IDO1) plays a key role in tumor immune evasion and inhibition of IDO1 is efficacious in preclinical models of breast cancer. As the response of breast cancer to immune checkpoint inhibitors may be limited, a better understanding of the expression of additional targetable immunomodulatory pathways is of importance. We therefore investigated the regulation of IDO1 expression in different breast cancer subtypes. We identified estrogen receptor α (ER) as a negative regulator of IDO1 expression...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344886/car-t-cell-intrinsic-pd-1-checkpoint-blockade-a-two-in-one-approach-for-solid-tumor-immunotherapy
#10
Nan Chen, Aurore Morello, Zachary Tano, Prasad S Adusumilli
PD-L1/2 expression in solid tumors inhibits chimeric antigen receptor (CAR) T-cell efficacy. A PD-1 dominant negative receptor expressed in CAR T cells provides cell-intrinsic checkpoint blockade and augments antitumor efficacy. A combinatorial immunotherapeutic strategy of combining CAR T cells with checkpoint blockade is a promising treatment approach for solid tumors.
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344878/targeting-cytokine-signaling-checkpoint-cis-activates-nk-cells-to-protect-from-tumor-initiation-and-metastasis
#11
Eva M Putz, Camille Guillerey, Kevin Kos, Kimberley Stannard, Kim Miles, Rebecca B Delconte, Kazuyoshi Takeda, Sandra E Nicholson, Nicholas D Huntington, Mark J Smyth
The cytokine-induced SH2-containing protein CIS belongs to the suppressor of cytokine signaling (SOCS) protein family. Here, we show the critical role of CIS in suppressing natural killer (NK) cell control of tumor initiation and metastasis. Cish-deficient mice were highly resistant to methylcholanthrene-induced sarcoma formation and protected from lung metastasis of B16F10 melanoma and RM-1 prostate carcinoma cells. In contrast, the growth of primary subcutaneous tumors, including those expressing the foreign antigen OVA, was unchanged in Cish-deficient mice...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344871/description-of-the-immune-microenvironment-of-chondrosarcoma-and-contribution-to-progression
#12
François A Simard, Iseulys Richert, Alexandra Vandermoeten, Anne-Valérie Decouvelaere, Jean-Philippe Michot, Christophe Caux, Jean-Yves Blay, Aurélie Dutour
Chondrosarcoma (CHS) is a rare bone malignancy characterized by its resistance to conventional systemic and radiation therapies. Whether immunotherapy targeting immune checkpoints may be active in these tumors remains unknown. To explore the role of the immune system in this tumor, we analyzed the immune environment of chondrosarcomas both in human sample, and in a syngeneic rat model, and tested the contribution of T lymphocytes and macrophages in chondrosarcoma progression. Immunohistochemical stainings were performed on human chondrosarcoma samples and on Swarm rat chondrosarcoma (SRC) model...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344870/immunological-profiling-of-molecularly-classified-high-risk-endometrial-cancers-identifies-pole-mutant-and-microsatellite-unstable-carcinomas-as-candidates-for-checkpoint-inhibition
#13
Florine A Eggink, Inge C Van Gool, Alexandra Leary, Pamela M Pollock, Emma J Crosbie, Linda Mileshkin, Ekaterina S Jordanova, Julien Adam, Luke Freeman-Mills, David N Church, Carien L Creutzberg, Marco De Bruyn, Hans W Nijman, Tjalling Bosse
High-risk endometrial cancer (EC) is an aggressive disease for which new therapeutic options are needed. Aims of this study were to validate the enhanced immune response in highly mutated ECs and to explore immune profiles in other EC subgroups. We evaluated immune infiltration in 116 high-risk ECs from the TransPORTEC consortium, previously classified into four molecular subtypes: (i) ultramutated POLE exonuclease domain-mutant ECs (POLE-mutant); (ii) hypermutated microsatellite unstable (MSI); (iii) p53-mutant; and (iv) no specific molecular profile (NSMP)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344869/il-15-tim-3-and-nk-cells-subsets-predict-responsiveness-to-anti-ctla-4-treatment-in-melanoma-patients
#14
Rossana Tallerico, Costanza M Cristiani, Elina Staaf, Cinzia Garofalo, Rosa Sottile, Mariaelena Capone, Yago Pico de Coaña, Gabriele Madonna, Eleonora Palella, Maria Wolodarski, Valentina Carannante, Domenico Mallardo, Ester Simeone, Antonio M Grimaldi, Sofia Johansson, Paolo Frumento, Elio Gulletta, Andrea Anichini, Francesco Colucci, Gennaro Ciliberto, Rolf Kiessling, Klas Kärre, Paolo A Ascierto, Ennio Carbone
Despite the success of immune checkpoint blockade in melanoma, the majority of patients do not respond. We hypothesized that the T and NK cell subset frequencies and expression levels of their receptors may predict responses and clinical outcome of anti-CTLA-4 treatment. We thus characterized the NK and T cell phenotype, as well as serum levels of several cytokines in 67 melanoma patients recruited in Italy and Sweden, using samples drawn prior to and during treatment. Survival correlated with low expression of the inhibitory receptor TIM-3 on circulating T and NK cells prior to and during treatment and with the increased frequency of mature circulating NK cells (defined as CD3(-)CD56(dim) CD16(+)) during treatment...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344858/nab-paclitaxel-for-the-treatment-of-breast-cancer-an-update-across-treatment-settings
#15
REVIEW
Adam Brufsky
PURPOSE: The purpose of this systematic review is to discuss recent studies and ongoing trials of nab-paclitaxel in breast cancer and to examine the potential role of nab-paclitaxel as a backbone for immuno-oncology therapies. METHODS: PubMed and selected congress proceedings were searched for studies of nab-paclitaxel in breast cancer published between 2013 and 2015. All phase II and III clinical trials, retrospective analyses, and institutional studies were included...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28344809/basal-cell-carcinoma-pd-l1-pd-1-checkpoint-expression-and-tumor-regression-after-pd-1-blockade
#16
Evan J Lipson, Mohammed T Lilo, Aleksandra Ogurtsova, Jessica Esandrio, Haiying Xu, Patricia Brothers, Megan Schollenberger, William H Sharfman, Janis M Taube
Monoclonal antibodies that block immune regulatory proteins such as programmed death-1 (PD-1) have demonstrated remarkable efficacy in controlling the growth of multiple tumor types. Unresectable or metastatic basal cell carcinoma, however, has largely gone untested. Because PD-Ligand-1 (PD-L1) expression in other tumor types has been associated with response to anti-PD-1, we investigated the expression of PD-L1 and its association with PD-1 expression in the basal cell carcinoma tumor microenvironment. Among 40 basal cell carcinoma specimens, 9/40 (22%) demonstrated PD-L1 expression on tumor cells, and 33/40 (82%) demonstrated PD-L1 expression on tumor-infiltrating lymphocytes and associated macrophages...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28344807/ipilimumab-induced-thrombotic-thrombocytopenic-purpura-ttp
#17
Jeanelle King, Javier de la Cruz, Jose Lutzky
BACKGROUND: CTLA-4 (Cytotoxic T-lymphocyte-associated protein 4) was the first immune checkpoint receptor clinically targeted for use in cancer treatment. It is expressed exclusively on T-cells where its primary role is to regulate the amplitude of the early stages of T-cell activation.1 Ipilimumab, a CTLA-4 blocking antibody, has been widely used for the treatment of patients with high risk and metastatic melanoma. Given its mechanism of action and consequent immune activation, the side effect profile of this drug greatly differs from that of standard cytotoxic chemotherapy...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28344743/the-abscopal-effect-of-radiation-therapy-what-is-it-and-how-can-we-use-it-in-breast-cancer
#18
REVIEW
Zishuo I Hu, Heather L McArthur, Alice Y Ho
The abscopal effect refers to the ability of localized radiation to trigger systemic antitumor effects. Over the past 50 years, reports on the abscopal effect arising from conventional radiation have been relatively rare. However, with the continued development and use of immunotherapy strategies incorporating radiotherapy with targeted immunomodulators and immune checkpoint blockade, the abscopal effect is becoming increasingly relevant in less immunogenic tumors such as breast cancer. Here, we review the mechanism of the abscopal effect, the current preclinical and clinical data, and the application of the abscopal effect in designing clinical trials of immunotherapy combined with radiotherapy in breast cancer...
2017: Current Breast Cancer Reports
https://www.readbyqxmd.com/read/28344662/nivolumab-in-renal-cell-carcinoma-latest-evidence-and-clinical-potential
#19
REVIEW
Camille Mazza, Bernard Escudier, Laurence Albiges
Similar to melanoma, renal cell carcinoma (RCC) has been historically considered as an immunogenic tumor, with interleukin 2 (IL-2) and interferon alpha (IFN-α) being the first approved treatments in the 1990s. However, these therapies were effective in only 10-20% of cases and were not well tolerated. Recently, new insights on the interaction between the immune system and tumor have identified the programmed death-1/programmed death-ligand-1 (PD-1/PD-L1) pathway to be a key player in evading host immune responses...
March 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28343997/dna-double-strand-breaks-and-aurora-b-mislocalization-induced-by-exposure-of-early-mitotic-cells-to-h2o2-appear-to-increase-chromatin-bridges-and-resultant-cytokinesis-failure
#20
Min-Guk Cho, Ju-Hyun Ahn, Hee-Song Choi, Jae-Ho Lee
Aneuploidy, an abnormal number of chromosomes that is a hallmark of cancer cells, can arise from tetraploid/binucleated cells through a failure of cytokinesis. Reactive oxygen species (ROS) have been implicated in various diseases, including cancer. However, the nature and role of ROS in cytokinesis progression and related mechanisms has not been clearly elucidated. Here, using time-lapse analysis of asynchronously growing cells and immunocytochemical analyses of synchronized cells, we found that hydrogen peroxide (H2O2) treatment at early mitosis (primarily prometaphase) significantly induced cytokinesis failure...
March 24, 2017: Free Radical Biology & Medicine
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