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Journal for Immunotherapy of Cancer

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https://www.readbyqxmd.com/read/30086799/a-possible-new-pathway-in-natural-killer-cell-activation-also-reveals-the-difficulty-in-determining-human-nk-cell-function-in-cancer
#1
Robert J Canter, William J Murphy
Immunotherapy is rapidly becoming the fourth arm of cancer treatment, and breakthrough successes have been observed in multiple malignancies. However, despite the potential for impressive anti-tumor effects, on average, only 25% of patients respond, and barriers clearly remain. Hence, uncovering innovative ways to apply immunotherapy and overcome immune resistance remains an unmet need in immuno-oncology. Natural killer (NK) cells are an attractive candidate for extending the promise of immunotherapy, although success to date has been largely limited to hematological cancers...
August 7, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/30081947/white-paper-on-microbial-anti-cancer-therapy-and-prevention
#2
Neil S Forbes, Robert S Coffin, Liang Deng, Laura Evgin, Steve Fiering, Matthew Giacalone, Claudia Gravekamp, James L Gulley, Hal Gunn, Robert M Hoffman, Balveen Kaur, Ke Liu, Herbert Kim Lyerly, Ariel E Marciscano, Eddie Moradian, Sheryl Ruppel, Daniel A Saltzman, Peter J Tattersall, Steve Thorne, Richard G Vile, Halle Huihong Zhang, Shibin Zhou, Grant McFadden
In this White Paper, we discuss the current state of microbial cancer therapy. This paper resulted from a meeting ('Microbial Based Cancer Therapy') at the US National Cancer Institute in the summer of 2017. Here, we define 'Microbial Therapy' to include both oncolytic viral therapy and bacterial anticancer therapy. Both of these fields exploit tumor-specific infectious microbes to treat cancer, have similar mechanisms of action, and are facing similar challenges to commercialization. We designed this paper to nucleate this growing field of microbial therapeutics and increase interactions between researchers in it and related fields...
August 6, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/30064495/delayed-onset-of-neurosarcoidosis-after-concurrent-ipilimumab-nivolumab-therapy
#3
Irena Tan, Michael Malinzak, April K S Salama
BACKGROUND: Immune checkpoint inhibitors have transformed the treatment landscape for many cancers, including metastatic melanoma, but have also opened the door for a diverse variety of immune-related adverse effects. CASE PRESENTATION: We describe the first reported case of presumed neurosarcoidosis as an immune-related adverse effect that developed nearly a year after discontinuation of treatment with combination ipilimumab and nivolumab for recurrent metastatic melanoma...
July 31, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/30053905/a-multi-center-phase-ii-study-of-high-dose-interleukin-2-sequenced-with-vemurafenib-in-patients-with-braf-v600-mutation-positive-metastatic-melanoma
#4
Joseph I Clark, Jatinder Singh, Marc S Ernstoff, Christopher D Lao, Lawrence E Flaherty, Theodore F Logan, Brendan Curti, Sanjiv S Agarwala, Bret Taback, Lee Cranmer, Jose Lutzky, Theresa L Luna, Sandra Aung, David H Lawson
BACKGROUND: Preclinical studies suggest that BRAF inhibitors enhance anti-tumor immunity and antigen presentation. Combination BRAF inhibition with immunotherapy is an appealing therapeutic approach. We sequenced vemurafenib with HD IL-2 in patients with BRAF-mutated metastatic melanoma to improve long term outcomes. METHODS: Eligible patients were HD IL-2 eligible with metastatic BRAF V600 mutated melanoma. Cohort 1 was treatment naïve and received vemurafenib 960 mg BID for 6 weeks before HD IL-2...
July 27, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/30012210/the-society-for-immunotherapy-of-cancer-consensus-statement-on-immunotherapy-for-the-treatment-of-non-small-cell-lung-cancer-nsclc
#5
Julie R Brahmer, Ramaswamy Govindan, Robert A Anders, Scott J Antonia, Sarah Sagorsky, Marianne J Davies, Steven M Dubinett, Andrea Ferris, Leena Gandhi, Edward B Garon, Matthew D Hellmann, Fred R Hirsch, Shakuntala Malik, Joel W Neal, Vassiliki A Papadimitrakopoulou, David L Rimm, Lawrence H Schwartz, Boris Sepesi, Beow Yong Yeap, Naiyer A Rizvi, Roy S Herbst
Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for over 85% of all cases. Until recently, chemotherapy - characterized by some benefit but only rare durable responses - was the only treatment option for patients with NSCLC whose tumors lacked targetable mutations. By contrast, immune checkpoint inhibitors have demonstrated distinctly durable responses and represent the advent of a new treatment approach for patients with NSCLC. Three immune checkpoint inhibitors, pembrolizumab, nivolumab and atezolizumab, are now approved for use in first- and/or second-line settings for selected patients with advanced NSCLC, with promising benefit also seen in patients with stage III NSCLC...
July 17, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/30012216/baseline-neutrophil-to-lymphocyte-ratio-nlr-and-derived-nlr-could-predict-overall-survival-in-patients-with-advanced-melanoma-treated-with-nivolumab
#6
Mariaelena Capone, Diana Giannarelli, Domenico Mallardo, Gabriele Madonna, Lucia Festino, Antonio Maria Grimaldi, Vito Vanella, Ester Simeone, Miriam Paone, Giuseppe Palmieri, Ernesta Cavalcanti, Corrado Caracò, Paolo Antonio Ascierto
BACKGROUND: Previous studies have suggested that elevated neutrophil-to-lymphocyte ratio (NLR) is prognostic for worse outcomes in patients with a variety of solid cancers, including those treated with immune checkpoint inhibitors. METHODS: This was a retrospective analysis of 97 consecutive patients with stage IV melanoma who were treated with nivolumab. Baseline NLR and derived (d) NLR were calculated and, along with other characteristics, correlated with progression-free survival (PFS) and overall survival (OS) in univariate and multivariate analyses...
July 16, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/30012209/sick-sinus-syndrome-associated-with-anti-programmed-cell-death-1
#7
Chien-Yi Hsu, Yu-Wen Su, San-Chi Chen
BACKGROUND: Use of anti-programmed cell death-1 (anti-PD-1) has been successful in treating many types of cancers. Despite its promising efficacy, immune-related adverse events are still a major concern. Immune-related cardiotoxicity, which is rare but fatal, has recently become a focus of attention. Cardiotoxicities including myocarditis, cardiomyopathy, cardiac fibrosis, heart block and cardiac arrest have been reported. Of these toxicities, myocarditis is often accompanied by dysrhythmia...
July 16, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/30012206/severe-hemophagocytic-lymphohistiocytosis-in-a-melanoma-patient-treated-with-ipilimumab-nivolumab
#8
Andrew Hantel, Brooke Gabster, Jason X Cheng, Harvey Golomb, Thomas F Gajewski
BACKGROUND: Treatment of metastatic melanoma patients with immune checkpoint inhibitors is an important standard of care. Side effects are due to immune activation, can affect virtually all organ systems, and are occasionally severe. Although hematologic toxicity has been reported, we present a case of hemophagocytic lymphohistiocytosis (HLH) due to immune checkpoint inhibitor therapy. CASE PRESENTATION: A patient with metastatic melanoma was treated with one course of ipilimumab + nivolumab and presented 3 weeks later with severe anemia and hyperferritinemia...
July 16, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/30005714/cart-cells-are-prone-to-fas-and-dr5-mediated-cell-death
#9
Benjamin O Tschumi, Nina Dumauthioz, Bastien Marti, Lianjun Zhang, Pascal Schneider, Jean-Pierre Mach, Pedro Romero, Alena Donda
Adoptive transfer of T cells transduced with Chimeric Antigen Receptors (CAR) are now FDA-approved for the treatment of B-cell malignancies. Yet, the functionality of the endogenous TCR in CART cells has not been fully assessed. Here, we demonstrate that CART cells progressively upregulate Fas, FasL, DR5 and TRAIL, which result in their programmed cell death, independently of antigen-mediated TCR or CAR activation. CART cell apoptosis occurs even when the CAR contains a single (co-)activatory domain such as CD3ζ, CD28 or 4-1BB...
July 13, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/30001747/isolation-of-t-cell-receptors-targeting-recurrent-neoantigens-in-hematological-malignancies
#10
Vanessa M Tubb, Deborah S Schrikkema, Nathan P Croft, Anthony W Purcell, Carsten Linnemann, Manon R Freriks, Frederick Chen, Heather M Long, Steven P Lee, Gavin M Bendle
Mutation-derived neoantigens represent an important class of tumour-specific, tumour rejection antigens, and are attractive targets for TCR gene therapy of cancer. The majority of such mutations are patient-specific and targeting these requires a fully personalized approach. However, some mutations are found recurrently among cancer patients, and represent potential targets for neoantigen-specific TCR gene therapy that is more widely applicable. Therefore, we have investigated if some cancer mutations found recurrently in hematological malignancies encode immunogenic neoantigens presented by common European Caucasoid HLA class I alleles and can form targets for TCR gene therapy...
July 13, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29996921/salvage-pembrolizumab-added-to-kinase-inhibitor-therapy-for-the-treatment-of-anaplastic-thyroid-carcinoma
#11
Priyanka C Iyer, Ramona Dadu, Maria Gule-Monroe, Naifa L Busaidy, Renata Ferrarotto, Mouhammed Amir Habra, Mark Zafereo, Michelle D Williams, G Brandon Gunn, Horiana Grosu, Heath D Skinner, Erich M Sturgis, Neil Gross, Maria E Cabanillas
BACKGROUND: Anaplastic thyroid carcinoma (ATC) is a rare but deadly form of thyroid cancer. Kinase inhibitors kinase inhibitors have shown clinical efficacy in the management of ATC, however, eventually these tumors acquire resistance to KI and patients succumb to their disease. Salvage therapy in this setting is limited. As ATC tumors diffusely express the programmed cell death protein ligand (PD-L1), anti- programmed cell death protein (PD-1) drugs such as pembrolizumab offer therapeutic potential...
July 11, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29996914/perspectives-in-immunotherapy-meeting-report-from-the-immunotherapy-bridge-29-30-november-2017-naples-italy
#12
REVIEW
Paolo A Ascierto, James Brugarolas, Luigi Buonaguro, Lisa H Butterfield, David Carbone, Bruno Daniele, Robert Ferris, Bernard A Fox, Jérôme Galon, Cesare Gridelli, Howard L Kaufman, Christopher A Klebanoff, Ignacio Melero, Paul Nathan, Chrystal M Paulos, Marco Ruella, Ryan Sullivan, Hassane Zarour, Igor Puzanov
Immunotherapy represents the third important wave in the history of the systemic treatment of cancer after chemotherapy and targeted therapy and is now established as a potent and effective treatment option across several cancer types. The clinical success of anti-cytotoxic T-lymphocyte-associated antigen (CTLA)-4, first, and anti-programmed death (PD)-1/PD-ligand (L)1 agents in melanoma and other cancers a few years later, has encouraged increasing focus on the development of other immunotherapies (e.g. monoclonal antibodies with other immune targets, adoptive cell transfer, and vaccines), with over 3000 immuno-oncology trials ongoing, involving hundreds of research institutes across the globe...
July 11, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29986769/complete-response-to-ipilimumab-and-nivolumab-therapy-in-a-patient-with-extensive-extrapulmonary-high-grade-small-cell-carcinoma-of-the-pancreas-and-hiv-infection
#13
Muhammad Husnain, Wungki Park, Juan Carlos Ramos, Thomas E Johnson, Joseph Chan, Arvind Dasari, Raja Mudad, Peter J Hosein
BACKGROUND: Immune checkpoint inhibitors (CPIs) have shown promising results in many solid tumors. There are limited data on the safety and efficacy of these drugs in HIV infected patients as they have traditionally been excluded from CPIs clinical trials. CASE PRESENTATION: We present a case of an HIV-positive patient with extensive extrapulmonary high-grade small cell carcinoma who was treated with dual CPIs (nivolumab and ipilimumab) with a complete response to therapy and with a manageable safety profile...
July 9, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29986768/a-team-effort-natural-killer-cells-on-the-first-leg-of-the-tumor-immunity-relay-race
#14
EDITORIAL
Timothy B Fessenden, Ellen Duong, Stefani Spranger
Recent work by Böttcher and colleagues defines a new role for Natural Killer cells in the anti-tumor immune response, arriving early into the tumor microenvironment before passing the baton to DC1 dendritic cells. DC1 dendritic cells subsequently activate CD8+ T cells resulting in effective anti-tumor immunity. This work highlights the cooperative nature of anti-tumor immunity set in motion by Natural Killer cells, and immune evasion by tumors through their exclusion.
July 9, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29970158/tumor-matrix-remodeling-and-novel-immunotherapies-the-promise-of-matrix-derived-immune-biomarkers
#15
REVIEW
Muhammad Umair Mushtaq, Athanasios Papadas, Adam Pagenkopf, Evan Flietner, Zachary Morrow, Sibgha Gull Chaudhary, Fotis Asimakopoulos
Recent advances in our understanding of the dynamics of cellular cross-talk have highlighted the significance of host-versus-tumor effect that can be harnessed with immune therapies. Tumors exploit immune checkpoints to evade adaptive immune responses. Cancer immunotherapy has witnessed a revolution in the past decade with the development of immune checkpoint inhibitors (ICIs), monoclonal antibodies against cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) or their ligands, such as PD1 ligand 1 (PD-L1)...
July 3, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29966520/efficacy-of-metformin-in-combination-with-immune-checkpoint-inhibitors-anti-pd-1-anti-ctla-4-in-metastatic-malignant-melanoma
#16
Muhammad Zubair Afzal, Rima R Mercado, Keisuke Shirai
BACKGROUND: Metformin is one of the biguanides commonly used in patients with type II Diabetes Mellitus. Apart from its hypoglycemic properties, metformin also inhibits the cell cycle by restricting protein synthesis and cell proliferation via regulating the LKB1/AMPL pathway. Furthermore, it also enhances the PD-1 blockade through a reduction of tumor hypoxia. Metformin has shown a significant favorable impact on treatment-related outcomes in solid tumors, but these outcomes have not been replicated in the limited clinical studies done on malignant melanoma...
July 2, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29929551/pan-cancer-adaptive-immune-resistance-as-defined-by-the-tumor-inflammation-signature-tis-results-from-the-cancer-genome-atlas-tcga
#17
Patrick Danaher, Sarah Warren, Rongze Lu, Josue Samayoa, Amy Sullivan, Irena Pekker, Brett Wallden, Francesco M Marincola, Alessandra Cesano
The Tumor Inflammation Signature (TIS) is an investigational use only (IUO) 18-gene signature that measures a pre-existing but suppressed adaptive immune response within tumors. The TIS has been shown to enrich for patients who respond to the anti-PD1 agent pembrolizumab. To explore this immune phenotype within and across tumor types, we applied the TIS algorithm to over 9000 tumor gene expression profiles downloaded from The Cancer Genome Atlas (TCGA). As expected based on prior evidence, tumors with known clinical sensitivity to anti-programmed cell death protein 1 (PD-1) blockade had higher average TIS scores...
June 22, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29925431/inhibition-of-wee1-kinase-and-cell-cycle-checkpoint-activation-sensitizes-head-and-neck-cancers-to-natural-killer-cell-therapies
#18
Jay Friedman, Megan Morisada, Lillian Sun, Ellen C Moore, Michelle Padget, James W Hodge, Jeffrey Schlom, Sofia R Gameiro, Clint T Allen
BACKGROUND: Natural killer (NK) cells recognize and lyse target tumor cells in an MHC-unrestricted fashion and complement antigen- and MHC-restricted killing by T-lymphocytes. NK cells and T-lymphocytes mediate early killing of targets through a common granzyme B-dependent mechanism. Tumor cell resistance to granzyme B and how this alters NK cell killing is not clearly defined. METHODS: Tumor cell sensitivity to cultured murine KIL and human high affinity NK (haNK) cells in the presence or absence of AZD1775, a small molecule inhibitor of WEE1 kinase, was assessed via real time impedance analysis...
June 21, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29921320/phase-ia-study-of-the-indoleamine-2-3-dioxygenase-1-ido1-inhibitor-navoximod-gdc-0919-in-patients-with-recurrent-advanced-solid-tumors
#19
Asha Nayak-Kapoor, Zhonglin Hao, Ramses Sadek, Robin Dobbins, Lisa Marshall, Nicholas N Vahanian, W Jay Ramsey, Eugene Kennedy, Mario R Mautino, Charles J Link, Ray S Lin, Stephanie Royer-Joo, Xiaorong Liang, Laurent Salphati, Kari M Morrissey, Sami Mahrus, Bruce McCall, Andrea Pirzkall, David H Munn, John E Janik, Samir N Khleif
BACKGROUND: Indoleamine-2,3-dioxygenase 1 (IDO1) catalyzes the oxidation of tryptophan into kynurenine and is partially responsible for acquired immune tolerance associated with cancer. The IDO1 small molecule inhibitor navoximod (GDC-0919, NLG-919) is active as a combination therapy in multiple tumor models. METHODS: This open-label Phase Ia study assessed safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary anti-tumor activity of navoximod in patients with recurrent/advanced solid tumors, administered as 50-800 mg BID on a 21/28 day and at 600 mg on a 28/28 day schedule...
June 20, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29921314/oxidized-lipids-keep-heat-shock-chaperones-busy-new-insights-on-the-deficiencies-of-tumour-associated-dendritic-cells
#20
EDITORIAL
Paula Nunes-Hasler
In a recent publication in Nature Communications the group of Dr. Dmitry Gabrilovich takes us one step closer to understanding why lipid accumulation impairs the function of tumour-associated dendritic cells (DCs). In this study, the authors present two surprising and significant findings. First, they show that in mouse DCs oxidized lipids function as a sink that traps the heat shock chaperone HSP70, a molecular target of emerging anti-cancer strategies. Secondly, they find that HSP70 in turn regulates the trafficking of peptide-loaded major histocompatibility complex class I (pMHC-I) molecules, a complex that triggers the proliferation of cancer-killing T cells...
June 20, 2018: Journal for Immunotherapy of Cancer
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