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https://www.readbyqxmd.com/read/28936442/cardiotoxicity-of-cancer-chemotherapy-identification-prevention-and-treatment
#1
REVIEW
Diwakar Jain, Tauseef Ahmad, Mitchel Cairo, Wilbert Aronow
Cardiotoxicity is an important complication of several cancer therapeutic agents. Several well established and newer anticancer therapies such as anthracyclines, trastuzumab and other HER2 receptor blockers, antimetabolites, alkylating agents, tyrosine kinase inhibitors (TKIs), angiogenesis inhibitors, and checkpoint inhibitors are associated with significant cardiotoxicity. Cardiovascular imaging employing radionuclide imaging, echocardiography and magnetic resonance imaging are helpful in early detection and prevention of overt heart failure secondary to cardiotoxicity of cancer therapy...
September 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28932642/trex1-dictates-the-immune-fate-of-irradiated-cancer-cells
#2
Claire Vanpouille-Box, Silvia C Formenti, Sandra Demaria
The optimal radiation dose and fractionation to induce anti-tumor immunity remain elusive. We recently found that the exonuclease TREX1 abrogates the immunogenicity of irradiated cancer cells by degrading interferon-stimulatory cytosolic dsDNA. TREX1 upregulation by radiation dose per fraction beyond a threshold of 10-12 Gy results in poor synergy with immune checkpoint blockers.
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28928380/predictors-of-responses-to-immune-checkpoint-blockade-in-advanced-melanoma
#3
N Jacquelot, M P Roberti, D P Enot, S Rusakiewicz, N Ternès, S Jegou, D M Woods, A L Sodré, M Hansen, Y Meirow, M Sade-Feldman, A Burra, S S Kwek, C Flament, M Messaoudene, C P M Duong, L Chen, B S Kwon, A C Anderson, V K Kuchroo, B Weide, F Aubin, C Borg, S Dalle, O Beatrix, M Ayyoub, B Balme, G Tomasic, A M Di Giacomo, M Maio, D Schadendorf, I Melero, B Dréno, A Khammari, R Dummer, M Levesque, Y Koguchi, L Fong, M Lotem, M Baniyash, H Schmidt, I M Svane, G Kroemer, A Marabelle, S Michiels, A Cavalcanti, M J Smyth, J S Weber, A M Eggermont, L Zitvogel
Immune checkpoint blockers (ICB) have become pivotal therapies in the clinical armamentarium against metastatic melanoma (MMel). Given the frequency of immune related adverse events and increasing use of ICB, predictors of response to CTLA-4 and/or PD-1 blockade represent unmet clinical needs. Using a systems biology-based approach to an assessment of 779 paired blood and tumor markers in 37 stage III MMel patients, we analyzed association between blood immune parameters and the functional immune reactivity of tumor-infiltrating cells after ex vivo exposure to ICB...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28900678/socs1-regulator-of-t-cells-in-autoimmunity-and-cancer
#4
Subburaj Ilangumaran, Diwakar Bobbala, Sheela Ramanathan
SOCS1 is a negative feedback regulator of cytokine and growth factor receptor signaling, and plays an indispensable role in attenuating interferon gamma signaling. Studies on SOCS1-deficient mice have established a crucial role for SOCS1 in regulating CD8(+) T cell homeostasis. In the thymus, SOCS1 prevents thymocytes that had failed positive selection from surviving and expanding, ensures negative selection and prevents inappropriate developmental skewing toward the CD8 lineage. In the periphery, SOCS1 not only controls production of T cell stimulatory cytokines but also attenuates the sensitivity of CD8(+) T cells to synergistic cytokine stimulation and antigen non-specific activation...
September 13, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28900328/immune-checkpoint-blockers-and-ovarian-cancer
#5
REVIEW
Chinmoy K Bose
Although the idea, called "cancer immunotherapy," is very appealing and has previously been shown to work in several mouse models of cancer, it has in general been very difficult to translate cancer immunotherapy approaches to humans. Because of this frustration, by the 1990s, many scientists and biotechnology companies had given up on the idea of cancer immunotherapy. After few years, first detection T-cell suppression of effect of cytotoxic T-lymphocyte antigen-4 (CTLA4) molecule was established. Antibody (Ab) to CTLA4 could increase T-cell starting a completely new age of tumor immunology...
April 2017: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/28878676/pd-1-and-pd-l1-checkpoint-signaling-inhibition-for-cancer-immunotherapy-mechanism-combinations-and-clinical-outcome
#6
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/28834216/beyond-the-m-csf-receptor-novel-therapeutic-targets-in-tumor-associated-macrophages
#7
REVIEW
Stefano Bonelli, Xenia Geeraerts, Evangelia Bolli, Jiri Keirsse, Maté Kiss, Ana Rita Pombo Antunes, Helena Van Damme, Karen De Vlaminck, Kiavash Movahedi, Damya Laoui, Geert Raes, Jo A Van Ginderachter
Tumor-associated macrophages (TAM) are by now established as important regulators of tumor progression by impacting on tumor immunity, angiogenesis and metastasis. Hence, a multitude of approaches are currently pursued to intervene with TAM's protumor activities, the most advanced of which being a blockade of M-CSF/M-CSFR signaling. M-CSFR signaling largely impacts on the differentiation of macrophages, including TAM, and hence strongly influences the numbers of these cells in tumors. However, a repolarization of TAM towards a more antitumor phenotype may be more elegant and may yield stronger effects on tumor growth...
August 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28822058/immune-dysfunction-in-non-hodgkin-lymphoma-avenues-for-new-immunotherapy-based-strategies
#8
REVIEW
Lorenzo Falchi
PURPOSE OF THIS REVIEW: The present review focuses on key aspects of non-Hodgkin lymphoma (NHL) evasion of immune surveillance and how these can be leveraged to devise effective immunotherapy strategies. RECENT FINDINGS: In recent years, significant progress has been made in the field of cancer immunotherapy. In particular, the remarkable clinical results of anti-programmed death (PD)-1/PD-ligand (L)1 antibodies are revolutionizing the treatment approach to multiple solid and hematologic tumors...
August 18, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28819022/%C3%AE-adrenergic-signaling-in-mice-housed-at-standard-temperatures-suppresses-an-effector-phenotype-in-cd8-t-cells-and-undermines-checkpoint-inhibitor-therapy
#9
Mark J Bucsek, Guanxi Qiao, Cameron R MacDonald, Thejaswini Giridharan, Lauren Evans, Brian Niedzwecki, Haichao Liu, Kathleen M Kokolus, Jason W-L Eng, Michelle N Messmer, Kristopher Attwood, Scott I Abrams, Bonnie L Hylander, Elizabeth A Repasky
The immune context of tumors has significant prognostic value and is predictive of responsiveness to several forms of therapy, including immunotherapy. We report here that CD8(+) T cell frequency and functional orientation within the tumor microenvironment is regulated by β2-adrenergic receptor (β-AR) signaling in host immune cells. We used three strategies - physiologic (manipulation of ambient thermal environment), pharmacologic (β-blockers), and genetic (β2-adrenergic receptor knockout mice) to reduce adrenergic stress signaling in two widely studied preclinical mouse tumor models...
August 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28811970/trial-watch-dendritic-cell-based-anticancer-immunotherapy
#10
REVIEW
Abhishek D Garg, Monica Vara Perez, Marco Schaaf, Patrizia Agostinis, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi
Dendritic cell (DC)-based vaccines against cancer have been extensively developed over the past two decades. Typically DC-based cancer immunotherapy entails loading patient-derived DCs with an appropriate source of tumor-associated antigens (TAAs) and efficient DC stimulation through a so-called "maturation cocktail" (typically a combination of pro-inflammatory cytokines and Toll-like receptor agonists), followed by DC reintroduction into patients. DC vaccines have been documented to (re)activate tumor-specific T cells in both preclinical and clinical settings...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28775144/a-bifunctional-mapk-pi3k-antagonist-for-inhibition-of-tumor-growth-and-metastasis
#11
Stefanie Galbán, April A Apfelbaum, Carlos Espinoza, Kevin Heist, Henry Haley, Karan Bedi, Mats Ljungman, Craig J Galbán, Gary D Luker, Marcian Van Dort, Brian D Ross
Responses to targeted therapies frequently are brief with patients relapsing with drug resistant tumors. For oncogenic MEK and BRAF inhibition, drug resistance commonly occurs through activation of PI3K/AKT/mTOR signaling and immune checkpoint modulation, providing a robust molecular target for concomitant therapy. Here, we evaluated the efficacy of a bifunctional kinase inhibitor (ST-162) that concurrently targets MAPK and PI3K signaling pathways. Treatment with ST-162 produced regression of mutant KRAS or BRAF addicted xenograft models of colorectal cancer and melanoma and stasis of BRAF/PTEN mutant melanomas...
August 3, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28756137/survival-of-patients-with-advanced-metastatic-melanoma-the-impact-of-novel-therapies-update-2017
#12
REVIEW
Selma Ugurel, Joachim Röhmel, Paolo A Ascierto, Keith T Flaherty, Jean Jacques Grob, Axel Hauschild, James Larkin, Georgina V Long, Paul Lorigan, Grant A McArthur, Antoni Ribas, Caroline Robert, Dirk Schadendorf, Claus Garbe
The treatment of metastatic melanoma is still undergoing a process of major change. The two most important novel therapeutic strategies, selective kinase inhibitors and immune checkpoint blockers, both significantly prolong survival times of patients with advanced metastatic disease. Different agents, dose regimens and combinations have been tested against each other vigorously within these two groups. However, results from prospective head-to-head comparative studies of both strategies are still lacking. We performed an exploratory analysis of survival data from selected clinical trials representative for the new treatment strategies in advanced metastatic melanoma...
September 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28751442/towards-precision-radiotherapy-for-use-with-immune-checkpoint-blockers
#13
Claire Vanpouille-Box, Silvia C Formenti, Sandra Demaria
The first evidence that radiation therapy (RT) enhances the efficacy of immune checkpoint blockers (ICBs) was obtained a dozen years ago in a mouse model of metastatic carcinoma refractory to anti-CTLA-4 treatment. At the time, ICBs had just entered clinical testing, an endeavor that culminated in 2011 with the approval of the first anti-CTLA-4 antibody for use in metastatic melanoma patients (ipilimumab). Thereafter, some patients progressing on ipilimumab showed systemic responses only upon receiving radiation to one lesion, confirming clinically the pro-immunogenic effects of radiation...
July 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28741900/the-avidity-of-tumor-specific-t-cells-amplified-by-a-pdc-based-assay-can-predict-the-clinical-evolution-of-melanoma-patients
#14
Julie Charles, Laurence Chaperot, Bruno Revol, Marine Baudin, Stephane Mouret, Agnes Hamon, Marie-Therese Leccia, Joel Plumas, Caroline Aspord
The advent of immune-checkpoint blockers and targeted therapies has changed the outcome of melanoma. However, many patients experience relapses, emphasizing the need for predictive and prognostic biomarkers. We developed a strategy based on plasmacytoid dendritic cells (pDCs) loaded with melanoma-tumor antigens that allows eliciting highly efficient antitumor T-cell responses. We used it to investigate antitumor T-cell functionality in peripheral blood mononuclear cells and tumor-infiltrating lymphocytes from melanoma patients...
July 25, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28741502/immune-priming-of-the-tumor-microenvironment-by-radiation
#15
REVIEW
Wen Jiang, Charles K Chan, Irving L Weissman, Betty Y S Kim, Stephen M Hahn
Ionizing irradiation can induce a multitude of alterations within the tumor microenvironment. Unlike targeted therapies, radiation delivered to the tumor bed can prompt phenotypic changes in both normal stromal and cancer cells, leading to molecular and physiological alterations within the tumor microenvironment. These environmental modulations directly influence the degree of immunogenicity of the tumor microenvironment and may ultimately affect tumor responsiveness to cancer immunotherapies. Here we review the preclinical evidence for tumor microenvironment-mediated immune suppression and how radiation can modulate immune properties within a tumor...
November 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28680746/novel-immune-checkpoint-blocker-to-treat-merkel-cell-carcinoma
#16
Lorenzo Galluzzi, Guido Kroemer
No abstract text is available yet for this article.
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28674473/cancer-immunotherapy-part-2-efficacy-safety-and-other-clinical-considerations
#17
C Lee Ventola
This article, the second in a series of three, provides an overview of the efficacy and safety of cancer immunotherapies ranging from monoclonal antibodies to vaccines, including additional clinical considerations regarding immune checkpoint blockers.
July 2017: P & T: a Peer-reviewed Journal for Formulary Management
https://www.readbyqxmd.com/read/28585615/-the-role-of-immunotherapy-in-the-modern-treatment-of-urothelial-carcinoma
#18
Anikó Maráz, Lajos Géczi
By the emergence of modern immunotherapies with active agents like PD-1 (nivolumab, pembrolizumab) and PD-L1 immune checkpoint blockers (atezolizumab, avelumab, durvalumab), new therapeutic options have become available for the treatment of patients with locally advanced and metastatic urothelial carcinoma. According to the recent publications, they have been effective in case of progression after platinum therapy, in or after second-line and in firstline therapies for cisplatin ineligible patients, respectively...
June 6, 2017: Magyar Onkologia
https://www.readbyqxmd.com/read/28551360/immunotherapeutic-properties-of-chemotherapy
#19
REVIEW
Carole Fournier, Thaiz Rivera Vargas, Tiffany Martin, Andréa Melis, Lionel Apetoh
Impressive remissions driven by immunological checkpoint blockade in cancer patients have prompted the scientific community to investigate afresh the crosstalk between cancer cells and the patient's immune system. Preclinical and clinical studies have highlighted that the anticancer efficacy of some conventional chemotherapeutics is based on their ability to restore anticancer immune responses. The current challenge is to understand and circumvent immune resistance mechanisms to chemo- and immunotherapies to design relevant immunotherapy and chemotherapy combinations...
May 24, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28546756/new-developments-in-the-treatment-of-advanced-squamous-cell-lung-cancer-focus-on-afatinib
#20
REVIEW
Vera Hirsh
Until recently, few treatment options existed for the treatment of squamous cell carcinoma (SqCC) of the lung, especially in the second-line setting following platinum-based chemotherapy. Accordingly, outcomes in this subtype of non-small-cell lung cancer (NSCLC) were generally poor. In this context, the recent availability of the checkpoint inhibitors nivolumab and pembrolizumab, the anti-VEGFR2 antibody ramucirumab (combined with docetaxel), and the ErbB-family blocker afatinib for the treatment of relapsed/refractory SqCC of the lung represent major advances...
2017: OncoTargets and Therapy
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