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ImmunoRx

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27 papers 0 to 25 followers
https://www.readbyqxmd.com/read/29255057/bifidobacterium-can-mitigate-intestinal-immunopathology-in-the-context-of-ctla-4-blockade
#1
Feng Wang, Qian Yin, Liang Chen, Mark M Davis
Antibodies that attenuate immune tolerance have been used to effectively treat cancer, but they can also trigger severe autoimmunity. To investigate this, we combined anti-CTLA-4 treatment with a standard colitis model to give mice a more severe form of the disease. Pretreatment with an antibiotic, vancomycin, provoked an even more severe, largely fatal form, suggesting that a Gram-positive component of the microbiota had a mitigating effect. We then found that a commonly used probiotic, Bifidobacterium, could largely rescue the mice from immunopathology without an apparent effect on antitumor immunity, and this effect may be dependent on regulatory T cells...
January 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29097493/gut-microbiome-modulates-response-to-anti-pd-1-immunotherapy-in-melanoma-patients
#2
V Gopalakrishnan, C N Spencer, L Nezi, A Reuben, M C Andrews, T V Karpinets, P A Prieto, D Vicente, K Hoffman, S C Wei, A P Cogdill, L Zhao, C W Hudgens, D S Hutchinson, T Manzo, M Petaccia de Macedo, T Cotechini, T Kumar, W S Chen, S M Reddy, R Szczepaniak Sloane, J Galloway-Pena, H Jiang, P L Chen, E J Shpall, K Rezvani, A M Alousi, R F Chemaly, S Shelburne, L M Vence, P C Okhuysen, V B Jensen, A G Swennes, F McAllister, E Marcelo Riquelme Sanchez, Y Zhang, E Le Chatelier, L Zitvogel, N Pons, J L Austin-Breneman, L E Haydu, E M Burton, J M Gardner, E Sirmans, J Hu, A J Lazar, T Tsujikawa, A Diab, H Tawbi, I C Glitza, W J Hwu, S P Patel, S E Woodman, R N Amaria, M A Davies, J E Gershenwald, P Hwu, J E Lee, J Zhang, L M Coussens, Z A Cooper, P A Futreal, C R Daniel, N J Ajami, J F Petrosino, M T Tetzlaff, P Sharma, J P Allison, R R Jenq, J A Wargo
Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti-programmed cell death 1 protein (PD-1) immunotherapy ( n = 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patient fecal microbiome samples ( n = 43, 30 responders, 13 nonresponders) showed significantly higher alpha diversity ( P < 0...
January 5, 2018: Science
https://www.readbyqxmd.com/read/29097494/gut-microbiome-influences-efficacy-of-pd-1-based-immunotherapy-against-epithelial-tumors
#3
Bertrand Routy, Emmanuelle Le Chatelier, Lisa Derosa, Connie P M Duong, Maryam Tidjani Alou, Romain Daillère, Aurélie Fluckiger, Meriem Messaoudene, Conrad Rauber, Maria P Roberti, Marine Fidelle, Caroline Flament, Vichnou Poirier-Colame, Paule Opolon, Christophe Klein, Kristina Iribarren, Laura Mondragón, Nicolas Jacquelot, Bo Qu, Gladys Ferrere, Céline Clémenson, Laura Mezquita, Jordi Remon Masip, Charles Naltet, Solenn Brosseau, Coureche Kaderbhai, Corentin Richard, Hira Rizvi, Florence Levenez, Nathalie Galleron, Benoit Quinquis, Nicolas Pons, Bernhard Ryffel, Véronique Minard-Colin, Patrick Gonin, Jean-Charles Soria, Eric Deutsch, Yohann Loriot, François Ghiringhelli, Gérard Zalcman, François Goldwasser, Bernard Escudier, Matthew D Hellmann, Alexander Eggermont, Didier Raoult, Laurence Albiges, Guido Kroemer, Laurence Zitvogel
Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis induce sustained clinical responses in a sizable minority of cancer patients. We found that primary resistance to ICIs can be attributed to abnormal gut microbiome composition. Antibiotics inhibited the clinical benefit of ICIs in patients with advanced cancer. Fecal microbiota transplantation (FMT) from cancer patients who responded to ICIs into germ-free or antibiotic-treated mice ameliorated the antitumor effects of PD-1 blockade, whereas FMT from nonresponding patients failed to do so...
January 5, 2018: Science
https://www.readbyqxmd.com/read/26612936/immunotherapy-could-microbial-therapy-boost-cancer-immunotherapy
#4
COMMENT
Alexandra Snyder, Eric Pamer, Jedd Wolchok
No abstract text is available yet for this article.
November 27, 2015: Science
https://www.readbyqxmd.com/read/29319049/mechanisms-of-resistance-to-immune-checkpoint-inhibitors
#5
REVIEW
Russell W Jenkins, David A Barbie, Keith T Flaherty
Immune checkpoint inhibitors (ICI) targeting CTLA-4 and the PD-1/PD-L1 axis have shown unprecedented clinical activity in several types of cancer and are rapidly transforming the practice of medical oncology. Whereas cytotoxic chemotherapy and small molecule inhibitors ('targeted therapies') largely act on cancer cells directly, immune checkpoint inhibitors reinvigorate anti-tumour immune responses by disrupting co-inhibitory T-cell signalling. While resistance routinely develops in patients treated with conventional cancer therapies and targeted therapies, durable responses suggestive of long-lasting immunologic memory are commonly seen in large subsets of patients treated with ICI...
January 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29316944/car-t-cells-targeting-cll-1-as-an-approach-to-treat-acute-myeloid-leukemia
#6
Jinghua Wang, Siyu Chen, Wei Xiao, Wende Li, Liang Wang, Shuo Yang, Weida Wang, Liping Xu, Shuangye Liao, Wenjian Liu, Yang Wang, Nawei Liu, Jianeng Zhang, Xiaojun Xia, Tiebang Kang, Gong Chen, Xiuyu Cai, Han Yang, Xing Zhang, Yue Lu, Penghui Zhou
BACKGROUND: Acute myeloid leukemia (AML) is one of the most common types of adult acute leukemia. Standard chemotherapies can induce complete remission in selected patients; however, a majority of patients eventually relapse and succumb to the disease. Thus, the development of novel therapeutics for AML is urgently needed. Human C-type lectin-like molecule-1 (CLL-1) is a type II transmembrane glycoprotein, and its expression is restricted to myeloid cells and the majority of AML blasts...
January 10, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28891423/adjuvant-nivolumab-versus-ipilimumab-in-resected-stage-iii-or-iv-melanoma
#7
RANDOMIZED CONTROLLED TRIAL
Jeffrey Weber, Mario Mandala, Michele Del Vecchio, Helen J Gogas, Ana M Arance, C Lance Cowey, Stéphane Dalle, Michael Schenker, Vanna Chiarion-Sileni, Ivan Marquez-Rodas, Jean-Jacques Grob, Marcus O Butler, Mark R Middleton, Michele Maio, Victoria Atkinson, Paola Queirolo, Rene Gonzalez, Ragini R Kudchadkar, Michael Smylie, Nicolas Meyer, Laurent Mortier, Michael B Atkins, Georgina V Long, Shailender Bhatia, Celeste Lebbé, Piotr Rutkowski, Kenji Yokota, Naoya Yamazaki, Tae M Kim, Veerle de Pril, Javier Sabater, Anila Qureshi, James Larkin, Paolo A Ascierto
BACKGROUND: Nivolumab and ipilimumab are immune checkpoint inhibitors that have been approved for the treatment of advanced melanoma. In the United States, ipilimumab has also been approved as adjuvant therapy for melanoma on the basis of recurrence-free and overall survival rates that were higher than those with placebo in a phase 3 trial. We wanted to determine the efficacy of nivolumab versus ipilimumab for adjuvant therapy in patients with resected advanced melanoma. METHODS: In this randomized, double-blind, phase 3 trial, we randomly assigned 906 patients (≥15 years of age) who were undergoing complete resection of stage IIIB, IIIC, or IV melanoma to receive an intravenous infusion of either nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks (453 patients) or ipilimumab at a dose of 10 mg per kilogram every 3 weeks for four doses and then every 12 weeks (453 patients)...
November 9, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28129122/phase-1-results-of-zuma-1-a-multicenter-study-of-kte-c19-anti-cd19-car-t-cell-therapy-in-refractory-aggressive-lymphoma
#8
MULTICENTER STUDY
Frederick L Locke, Sattva S Neelapu, Nancy L Bartlett, Tanya Siddiqi, Julio C Chavez, Chitra M Hosing, Armin Ghobadi, Lihua E Budde, Adrian Bot, John M Rossi, Yizhou Jiang, Allen X Xue, Meg Elias, Jeff Aycock, Jeff Wiezorek, William Y Go
Outcomes for patients with refractory diffuse large B cell lymphoma (DLBCL) are poor. In the multicenter ZUMA-1 phase 1 study, we evaluated KTE-C19, an autologous CD3ζ/CD28-based chimeric antigen receptor (CAR) T cell therapy, in patients with refractory DLBCL. Patients received low-dose conditioning chemotherapy with concurrent cyclophosphamide (500 mg/m2 ) and fludarabine (30 mg/m2 ) for 3 days followed by KTE-C19 at a target dose of 2 × 106 CAR T cells/kg. The incidence of dose-limiting toxicity (DLT) was the primary endpoint...
January 4, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28280247/t-cell-costimulatory-receptor-cd28-is-a-primary-target-for-pd-1-mediated-inhibition
#9
Enfu Hui, Jeanne Cheung, Jing Zhu, Xiaolei Su, Marcus J Taylor, Heidi A Wallweber, Dibyendu K Sasmal, Jun Huang, Jeong M Kim, Ira Mellman, Ronald D Vale
Programmed cell death-1 (PD-1) is a coinhibitory receptor that suppresses T cell activation and is an important cancer immunotherapy target. Upon activation by its ligand PD-L1, PD-1 is thought to suppress signaling through the T cell receptor (TCR). By titrating PD-1 signaling in a biochemical reconstitution system, we demonstrate that the co-receptor CD28 is strongly preferred over the TCR as a target for dephosphorylation by PD-1-recruited Shp2 phosphatase. We also show that CD28, but not the TCR, is preferentially dephosphorylated in response to PD-1 activation by PD-L1 in an intact cell system...
March 31, 2017: Science
https://www.readbyqxmd.com/read/28685821/pd-1-pd-l1-inhibitors-in-haematological-malignancies-update-2017
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
COMMENT
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
#18
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
#19
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
#20
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
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