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ImmunoRx

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18 papers 0 to 25 followers
https://www.readbyqxmd.com/read/28685821/pd-1-pd-l1-inhibitors-in-haematological-malignancies-update-2017
#1
REVIEW
Tomas Jelinek, Jana Mihalyova, Michal Kascak, Juraj Duras, Roman Hajek
The introduction of PD-1/PD-L1 pathway inhibitors is an important landmark in solid oncology with unprecedented practice-changing activity in various types of solid tumours. Among haematological malignancies, PD-1/PD-L1 inhibitors have been successful, so far, only in the treatment of classical Hodgkin lymphoma, which typically exhibits an over-expression of PD-1 ligands (PD-L1, PD-L2) due to alterations in chromosome 9p24.1. Such positive outcomes led to the US Food and Drug Administration approval of nivolumab use in relapsed Hodgkin lymphoma in 2016 as the first haematological indication...
November 2017: Immunology
https://www.readbyqxmd.com/read/28482851/checkpoint-inhibitors-in-hematological-malignancies
#2
REVIEW
Chi Young Ok, Ken H Young
Inhibitory molecules such as PD-1, CTLA-4, LAG-3, or TIM-3 play a role to keep a balance in immune function. However, many cancers exploit such molecules to escape immune surveillance. Accumulating data support that their functions are dysregulated in lymphoid neoplasms, including plasma cell myeloma, myelodysplastic syndrome, and acute myeloid leukemia. In lymphoid neoplasms, aberrations in 9p24.1 (PD-L1, PD-L2, and JAK2 locus), latent Epstein-Barr virus infection, PD-L1 3'-untranslated region disruption, and constitutive JAK-STAT pathway are known mechanisms to induce PD-L1 expression in lymphoma cells...
May 8, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28475571/is-autoimmunity-the-achilles-heel-of-cancer-immunotherapy
#3
Carl H June, Jeremy T Warshauer, Jeffrey A Bluestone
The emergence of immuno-oncology as the first broadly successful strategy for metastatic cancer will require clinicians to integrate this new pillar of medicine with chemotherapy, radiation, and targeted small-molecule compounds. Of equal importance is gaining an understanding of the limitations and toxicities of immunotherapy. Immunotherapy was initially perceived to be a relatively less toxic approach to cancer treatment than other available therapies-and surely it is, when compared to those. However, as the use of immunotherapy becomes more common, especially as first- and second-line treatments, immunotoxicity and autoimmunity are emerging as the Achilles' heel of immunotherapy...
May 5, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28280249/rescue-of-exhausted-cd8-t-cells-by-pd-1-targeted-therapies-is-cd28-dependent
#4
Alice O Kamphorst, Andreas Wieland, Tahseen Nasti, Shu Yang, Ruan Zhang, Daniel L Barber, Bogumila T Konieczny, Candace Z Daugherty, Lydia Koenig, Ke Yu, Gabriel L Sica, Arlene H Sharpe, Gordon J Freeman, Bruce R Blazar, Laurence A Turka, Taofeek K Owonikoko, Rathi N Pillai, Suresh S Ramalingam, Koichi Araki, Rafi Ahmed
Programmed cell death-1 (PD-1)-targeted therapies enhance T cell responses and show efficacy in multiple cancers, but the role of costimulatory molecules in this T cell rescue remains elusive. Here, we demonstrate that the CD28/B7 costimulatory pathway is essential for effective PD-1 therapy during chronic viral infection. Conditional gene deletion showed a cell-intrinsic requirement of CD28 for CD8 T cell proliferation after PD-1 blockade. B7-costimulation was also necessary for effective PD-1 therapy in tumor-bearing mice...
March 31, 2017: Science
https://www.readbyqxmd.com/read/27919908/targeting-the-pd-1-pd-l1-axis-in-multiple-myeloma-a-dream-or-a-reality
#5
REVIEW
Jacalyn Rosenblatt, David Avigan
The programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway is a negative regulator of immune activation that is upregulated in multiple myeloma and is a critical component of the immunosuppressive tumor microenvironment. Expression is increased in advanced disease and in the presence of bone marrow stromal cells. PD-1/PD-L1 blockade is associated with tumor regression in several malignancies, but single-agent activity is limited in myeloma patients. Combination therapy involving strategies to expand myeloma-specific T cells and T-cell activation via PD-1/PD-L1 blockade are currently being explored...
January 19, 2017: Blood
https://www.readbyqxmd.com/read/28153603/high-programmed-death-1-expression-on-t-cells-in-aplastic-anemia
#6
Wanhong Zhao, Yilin Zhang, Pengyu Zhang, Juan Yang, Longjin Zhang, Aili He, Wanggang Zhang, Tamura Hideto
Programmed death 1 (PD-1) has been reported to be associated with aberrant regulation of T cells activation in aplastic anemia (AA). However, the connection between PD-1 expression status and AA needs to be further explored. The aim of this study is to investigate PD-1 expression status on T cells in AA patients and to explore the effect of PD-1 on apoptosis of T cells and BMHSCs. The concentration of platelet, lymphocyte and hemoglobin in peripheral blood of AA patients and healthy volunteers was detected by automatic blood-counter system...
March 2017: Immunology Letters
https://www.readbyqxmd.com/read/27886124/advances-in-cancer-immunotherapy-in-solid-tumors
#7
REVIEW
Smitha Menon, Sarah Shin, Grace Dy
Immunotherapy is heralded as one of the most important advances in oncology. Until recently, only limited immunotherapeutic options were available in selected immunogenic cancers like melanoma and renal cell carcinomas. Nowadays, there is an improved understanding that anti-tumor immunity is controlled by a delicate balance in the tumor microenvironment between immune stimulatory and immune inhibitory pathways. Either by blocking the inhibitory pathways or stimulating the activating pathways that regulate cytotoxic lymphocytes, anti-tumor immunity can be enhanced leading to durable anti-tumor responses...
November 24, 2016: Cancers
https://www.readbyqxmd.com/read/27533008/pd-l2-elbows-out-pd-l1-to-rescue-t-cell-immunity-to-malaria
#8
Peter D Crompton, Susan K Pierce
How early interactions between innate and adaptive immune cells influence outcomes of acute infections is incompletely understood. In this issue of Immunity, Karunarathne et al. (2016) show that dendritic cells help CD4(+) T helper 1 cell immunity against malaria through PD-L2's competition with PD-L1.
August 16, 2016: Immunity
https://www.readbyqxmd.com/read/27533014/programmed-death-1-ligand-2-mediated-regulation-of-the-pd-l1-to-pd-1-axis-is-essential-for-establishing-cd4-t-cell-immunity
#9
Deshapriya S Karunarathne, Joshua M Horne-Debets, Johnny X Huang, Rebecca Faleiro, Chiuan Yee Leow, Fiona Amante, Thomas S Watkins, John J Miles, Patrick J Dwyer, Katryn J Stacey, Michael Yarski, Chek Meng Poh, Jason S Lee, Matthew A Cooper, Laurent Rénia, Derek Richard, James S McCarthy, Arlene H Sharpe, Michelle N Wykes
Many pathogens, including Plasmodium spp., exploit the interaction of programmed death-1 (PD-1) with PD-1-ligand-1 (PD-L1) to "deactivate" T cell functions, but the role of PD-L2 remains unclear. We studied malarial infections to understand the contribution of PD-L2 to immunity. Here we have shown that higher PD-L2 expression on blood dendritic cells, from Plasmodium falciparum-infected individuals, correlated with lower parasitemia. Mechanistic studies in mice showed that PD-L2 was indispensable for establishing effective CD4(+) T cell immunity against malaria, because it not only inhibited PD-L1 to PD-1 activity but also increased CD3 and inducible co-stimulator (ICOS) expression on T cells...
August 16, 2016: Immunity
https://www.readbyqxmd.com/read/27718847/pembrolizumab-versus-chemotherapy-for-pd-l1-positive-non-small-cell-lung-cancer
#10
RANDOMIZED CONTROLLED TRIAL
Martin Reck, Delvys Rodríguez-Abreu, Andrew G Robinson, Rina Hui, Tibor Csőszi, Andrea Fülöp, Maya Gottfried, Nir Peled, Ali Tafreshi, Sinead Cuffe, Mary O'Brien, Suman Rao, Katsuyuki Hotta, Melanie A Leiby, Gregory M Lubiniecki, Yue Shentu, Reshma Rangwala, Julie R Brahmer
BACKGROUND: Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased activity in tumors that express programmed death ligand 1 (PD-L1). METHODS: In this open-label, phase 3 trial, we randomly assigned 305 patients who had previously untreated advanced NSCLC with PD-L1 expression on at least 50% of tumor cells and no sensitizing mutation of the epidermal growth factor receptor gene or translocation of the anaplastic lymphoma kinase gene to receive either pembrolizumab (at a fixed dose of 200 mg every 3 weeks) or the investigator's choice of platinum-based chemotherapy...
November 10, 2016: New England Journal of Medicine
https://www.readbyqxmd.com/read/27501248/defining-cd8-t-cells-that-provide-the-proliferative-burst-after-pd-1-therapy
#11
Se Jin Im, Masao Hashimoto, Michael Y Gerner, Junghwa Lee, Haydn T Kissick, Matheus C Burger, Qiang Shan, J Scott Hale, Judong Lee, Tahseen H Nasti, Arlene H Sharpe, Gordon J Freeman, Ronald N Germain, Helder I Nakaya, Hai-Hui Xue, Rafi Ahmed
Chronic viral infections are characterized by a state of CD8(+) T-cell dysfunction that is associated with expression of the programmed cell death 1 (PD-1) inhibitory receptor. A better understanding of the mechanisms that regulate CD8(+) T-cell responses during chronic infection is required to improve immunotherapies that restore function in exhausted CD8(+) T cells. Here we identify a population of virus-specific CD8(+) T cells that proliferate after blockade of the PD-1 inhibitory pathway in mice chronically infected with lymphocytic choriomeningitis virus (LCMV)...
September 15, 2016: Nature
https://www.readbyqxmd.com/read/27620712/lung-cancer-first-line-immunotherapy-in-lung-cancer-taking-the-first-step
#12
Stephen V Liu, Giuseppe Giaccone
No abstract text is available yet for this article.
October 2016: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/27664133/targeting-immune-checkpoints-in-hematologic-malignancies
#13
REVIEW
Gheath Alatrash, Naval Daver, Elizabeth A Mittendorf
The use of antibodies that target immune checkpoint molecules on the surface of T-lymphocytes and/or tumor cells has revolutionized our approach to cancer therapy. Cytotoxic-T-lymphocyte antigen (CTLA-4) and programmed cell death protein 1 (PD-1) are the two most commonly targeted immune checkpoint molecules. Although the role of antibodies that target CTLA-4 and PD-1 has been established in solid tumor malignancies and Food and Drug Administration approved for melanoma and non-small cell lung cancer, there remains a desperate need to incorporate immune checkpoint inhibition in hematologic malignancies...
October 2016: Pharmacological Reviews
https://www.readbyqxmd.com/read/27448784/novel-approaches-in-cancer-immunotherapy-a-light-at-the-end-of-the-tunnel
#14
Monika Joshi, Sumanta K Pal, Joseph J Drabick
After decades of disappointments, the use of immunotherapy in cancer has finally come of age and resulted in a real paradigm shift in cancer treatment across many tumor types. With the advent of novel immunotherapies based on increasing understanding of the human immune system, cure has become a real possibility for many patients. The development of cancer vaccines, immune checkpoint inhibitors, chimeric antigen receptor T cell, oncolytic virus based immunotherapy to name a few have given hope to patients. One of the most exciting developments in the era of immunotherapy has been the discovery of checkpoint inhibitors causing blockade of two important immune pathways -- cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death receptor-1 (PD-1), resulting in empowerment of anti-tumor immunity...
June 2016: Discovery Medicine
https://www.readbyqxmd.com/read/26599172/cancer-immunotherapy-researchers-focus-on-refining-checkpoint-blockade-therapies
#15
Julie A Jacob
No abstract text is available yet for this article.
November 24, 2015: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/27365430/immunology-fighting-autoimmunity-with-immune-cells
#16
Mitch Leslie
No abstract text is available yet for this article.
July 1, 2016: Science
https://www.readbyqxmd.com/read/26977783/immunotherapy-pd-1-says-goodbye-tim-3-says-hello
#17
COMMENT
Diana Romero
No abstract text is available yet for this article.
April 2016: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/26541610/anticancer-immunotherapy-by-ctla-4-blockade-relies-on-the-gut-microbiota
#18
Marie Vétizou, Jonathan M Pitt, Romain Daillère, Patricia Lepage, Nadine Waldschmitt, Caroline Flament, Sylvie Rusakiewicz, Bertrand Routy, Maria P Roberti, Connie P M Duong, Vichnou Poirier-Colame, Antoine Roux, Sonia Becharef, Silvia Formenti, Encouse Golden, Sascha Cording, Gerard Eberl, Andreas Schlitzer, Florent Ginhoux, Sridhar Mani, Takahiro Yamazaki, Nicolas Jacquelot, David P Enot, Marion Bérard, Jérôme Nigou, Paule Opolon, Alexander Eggermont, Paul-Louis Woerther, Elisabeth Chachaty, Nathalie Chaput, Caroline Robert, Christina Mateus, Guido Kroemer, Didier Raoult, Ivo Gomperts Boneca, Franck Carbonnel, Mathias Chamaillard, Laurence Zitvogel
Antibodies targeting CTLA-4 have been successfully used as cancer immunotherapy. We find that the antitumor effects of CTLA-4 blockade depend on distinct Bacteroides species. In mice and patients, T cell responses specific for B. thetaiotaomicron or B. fragilis were associated with the efficacy of CTLA-4 blockade. Tumors in antibiotic-treated or germ-free mice did not respond to CTLA blockade. This defect was overcome by gavage with B. fragilis, by immunization with B. fragilis polysaccharides, or by adoptive transfer of B...
November 27, 2015: Science
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