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Immuno checkpoint

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https://www.readbyqxmd.com/read/28316970/dgk-%C3%AE-a-checkpoint-in-cancer-mediated-immuno-inhibition-and-target-for-immunotherapy
#1
Elfriede Noessner
Immunotherapy is moving to the forefront of cancer treatments owing to impressive durable responses achieved with checkpoint blockade antibodies and adoptive T-cell therapy. Still, improvements are necessary since, overall, only a small percentage of patients benefit from current therapies. Here, I summarize evidence that DGK-α may represent an immunological checkpoint suppressing the activity of cytotoxic immunocytes in the tumor microenvironment. DGK-inhibitors can restore the antitumor function of tumor-suppressed adaptive and innate cytotoxic immunocytes...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28302019/the-breakthroughs-in-cancer-immune-checkpoint-based-therapy-a-review-of-development-in-immune-checkpoint-study-and-its-application
#2
Yao Huang, Dong Liang, Jingfeng Liu, Jinhua Zeng, Yongyi Zeng
Recently, immunotherapy has attracted more attentions to fight cancer due to its selectivity, long lasting effects, and demonstrated better overall survival and tolerance, when compared to patients treated with conventional chemotherapy or radiotherapy alone. The anti-tumor response of patient with cancer is improved either by increasing the effector cell number, the production of soluble mediators, or by modulating the host's immune checkpoint. Over the last decades, many new approaches in immunotherapy have been developed, such as immune checkpoint inhibitors, chimeric antigen receptor T cells (CART), specific T-cell -receptor T cells (TCRT) and cancer vaccine, some of which has been approved by FDA to treat several cancer types...
March 15, 2017: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/28279470/novel-targeted-therapies-for-esophagogastric-cancer
#3
REVIEW
Steven B Maron, Daniel V T Catenacci
Gastroesophageal cancer (GEC) remains a major cause of cancer-related mortality worldwide. Although the incidence of distal gastric adenocarcinoma (GC) is declining in the United States, proximal esophagogastric junction adenocarcinoma (EGJ) is increasing in incidence. GEC, including GC and EGJ, is treated uniformly in the metastatic setting. Overall survival in the metastatic setting remains poor. Molecular characterization of GEC has identified mutations and copy number variations, along with other oncogenes, biomarkers, and immuno-oncologic checkpoints that may serve as actionable therapeutic targets...
April 2017: Surgical Oncology Clinics of North America
https://www.readbyqxmd.com/read/28277849/targeting-indolent-non-hodgkin-lymphoma
#4
Lori A Leslie, Alan P Skarbnik, Coleen Bejot, Susan Stives, Tatyana A Feldman, Andre H Goy
Due to recent advancements in the understanding of the molecular pathogenesis of B-cell malignancies, there has been an explosion of innovative agents in development. The purpose of this review is to efficiently summarize novel therapies with activity in indolent non-Hodgkin lymphoma (iNHL) targeting surface antigens, signaling pathways, and the tumor microenvironment. Areas covered: A literature search was performed to identify preclinical data and clinical trials focused on the use of targeted therapies in iNHL subtypes including follicular lymphoma, marginal zone lymphoma, small lymphocytic lymphoma, and lymphoplasmacytic lymphoma/Waldenström macroglobulinemia...
March 6, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28273064/class-iia-hdac-inhibition-reduces-breast-tumours-and-metastases-through-anti-tumour-macrophages
#5
Jennifer L Guerriero, Alaba Sotayo, Holly E Ponichtera, Jessica A Castrillon, Alexandra L Pourzia, Sara Schad, Shawn F Johnson, Ruben D Carrasco, Suzan Lazo, Roderick T Bronson, Scott P Davis, Mercedes Lobera, Michael A Nolan, Anthony Letai
Although the main focus of immuno-oncology has been manipulating the adaptive immune system, harnessing both the innate and adaptive arms of the immune system might produce superior tumour reduction and elimination. Tumour-associated macrophages often have net pro-tumour effects, but their embedded location and their untapped potential provide impetus to discover strategies to turn them against tumours. Strategies that deplete (anti-CSF-1 antibodies and CSF-1R inhibition) or stimulate (agonistic anti-CD40 or inhibitory anti-CD47 antibodies) tumour-associated macrophages have had some success...
March 8, 2017: Nature
https://www.readbyqxmd.com/read/28259887/hiv-associated-lung-cancer
#6
Til R Kiderlen, Jan Siehl, Marcus Hentrich
Lung cancer (LC) is one of the most common non-AIDS (acquired immune deficiency syndrome)-defining malignancies. It occurs more frequently in persons living with human immunodeficiency virus (PLWHIV) than in the HIV-negative population. Compared to their HIV-negative counterparts, patients are usually younger and diagnosed at more advanced stages. The pathogenesis of LC in PLWHIV is not fully understood, but immunosuppression in combination with chronic infection and the oncogenic effects of smoking and HIV itself all seem to play a role...
2017: Oncology Research and Treatment
https://www.readbyqxmd.com/read/28246276/interplay-between-immune-checkpoint-proteins-and-cellular-metabolism
#7
REVIEW
Sangbin Lim, Joshua B Phillips, Luciana Madeira da Silva, Ming Zhou, Oystein Fodstad, Laurie B Owen, Ming Tan
With the recent successes in immuno-oncology, renewed interest in the role of immune checkpoint modulators, such as the B7 family proteins, has escalated. The immune checkpoint proteins play a crucial role in the regulation of cellular immunity; however, their contribution to other aspects of cancer biology remains unclear. Accumulating evidence indicate that immune checkpoint proteins can regulate metabolic energetics of the tumor, the tumor microenvironment, and the tumor-specific immune response, leading to metabolic reprogramming of both malignant cells and immune cells involved in mounting and sustaining this response...
March 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28239470/fak-inhibition-opens-the-door-to-checkpoint-immunotherapy-in-pancreatic-cancer
#8
EDITORIAL
Stefan N Symeonides, Stephen M Anderton, Alan Serrels
Immunotherapy has had remarkable success in the treatment of some cancer types. However, pancreatic cancer has remained largely refractory to immunotherapy, including immune checkpoint inhibitors. Recently, Jiang and colleagues identified a key role for FAK in regulating the composition of the fibrotic and immuno-suppressive pancreatic tumour niche, and showed that FAK inhibitors can be used in combination with immune checkpoint blockade and gemcitabine chemotherapy to significantly delay pancreatic tumour progression...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28201977/targeting-the-immune-niche-within-the-bone-marrow-microenvironment-the-rise-of-immunotherapy-in-multiple-myeloma
#9
Klaus Podar, D Jäger
Multiple Myeloma (MM) cells inhibit the development of an effective anti-MM immune response via defects in T cell function, ineffective antigen presentation; reduced phagocytic capacity; natural killer and dendritic cell dysfunction; decreased responsiveness to IL-2 and defects in B cell immunity; upregulation of inhibitory pathways; and production of excessive pro-inflammatory cytokines. Moreover, immune cells including plasmacytoid dendritic cells and macrophages trigger tumor cell proliferation, survival, and drug resistance...
February 13, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28184224/cbl-b-deficiency-mediates-resistance-to-programmed-death-ligand-1-programmed-death-1-regulation
#10
Mai Fujiwara, Emily J Anstadt, Robert B Clark
Casitas B-lineage lymphoma-b (Cbl-b) is an E3 ubiquitin ligase that negatively regulates T cell activation. Cbl-b(-/-) T cells are hyper-reactive and co-stimulation independent, and Cbl-b(-/-) mice demonstrate robust T cell and NK cell-mediated antitumor immunity. As a result of these murine studies, Cbl-b is considered a potential target for therapeutic manipulation in human cancer immunotherapy. The PD-L1/PD-1 pathway of immune regulation is presently an important therapeutic focus in tumor immunotherapy, and although Cbl-b(-/-) mice have been shown to be resistant to several immuno-regulatory mechanisms, the sensitivity of Cbl-b(-/-) mice to PD-L1-mediated suppression has not been reported...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28167217/experimental-animal-modeling-for-immuno-oncology
#11
REVIEW
Qi-Xiang Li, Gerold Feuer, Xuesong Ouyang, Xiaoyu An
Immuno-oncology (I/O) research has intensified significantly in recent years due to the breakthrough development and the regulatory approval of several immune checkpoint inhibitors, leading to the rapid expansion of the new discovery of novel I/O therapies, new checkpoint inhibitors and beyond. However, many I/O questions remain unanswered, including why only certain subsets of patients respond to these treatments, who the responders would be, and how to expand patient response (the conversion of non-responders or maximizing response in partial responders)...
February 3, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28138031/anti-kit-monoclonal-antibody-treatment-enhances-the-anti-tumor-activity-of-immune-checkpoint-inhibitors-by-reversing-tumor-induced-immunosuppression
#12
Andrew J Garton, Scott Seibel, Lori Lopresti-Morrow, Linda Crew, Neal Janson, Sreekala Mandiyan, E Sergio Trombetta, Shannon Pankratz, Theresa M LaVallee, Richard Gedrich
The receptor tyrosine kinase KIT is an established oncogenic driver of tumor growth in certain tumor types including gastrointestinal stromal tumors (GIST), in which constitutively active mutant forms of KIT represent an actionable target for small molecule tyrosine kinase inhibitors. There is also considerable potential for KIT to influence tumor growth indirectly based on its expression and function in cell types of the innate immune system, most notably mast cells. We have evaluated syngeneic mouse tumor models for anti-tumor effects of an inhibitory KIT monoclonal antibody (mAb), dosed either alone or in combination with immune checkpoint inhibitors...
January 30, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28122590/pd-1-pd-l1-b7-h1-and-tumor-site-immune-modulation-therapy-the-historical-perspective
#13
REVIEW
Jun Wang, Ruirong Yuan, Wenru Song, Jingwei Sun, Delong Liu, Zihai Li
The current success of targeted inhibition against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed Death 1/Programmed Death Ligand 1 (PD-1/PD-L1, herein collectively referred to as PD) pathways is hailed as a cancer immunotherapy breakthrough. PD-L1, known also as B7 homolog 1 (B7-H1), was initially discovered by Dr. Lieping Chen in 1999. To recognize the seminal contributions by Chen to the development of PD-directed therapy against cancer, the Chinese American Hematologist and Oncologist Network (CAHON) decided to honor him with its inaugural Lifetime Achievement Award in Hematology and Oncology at the CAHON's 2015 annual meeting...
January 25, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28086852/pd-l1-expression-in-papillary-renal-cell-carcinoma
#14
Takanobu Motoshima, Yoshihiro Komohara, Chaoya Ma, Arni Kusuma Dewi, Hirotsugu Noguchi, Sohsuke Yamada, Toshiyuki Nakayama, Shohei Kitada, Yoshiaki Kawano, Wataru Takahashi, Masaaki Sugimoto, Motohiro Takeya, Naohiro Fujimoto, Yoshinao Oda, Masatoshi Eto
BACKGROUND: The immune escape or tolerance of cancer cells is considered to be closely involved in cancer progression. Programmed death-1 (PD-1) is an inhibitory receptor expressed on activating T cells, and several types of cancer cells were found to express PD-1 ligand 1 (PD-L1) and ligand 2 (PD-L2). METHODS: In the present study, we investigated PD-L1/2 expression in papillary renal cell carcinoma (pRCC). RESULT: We found PD-L1 expression in 29 of 102 cases, but no PD-L2 expression was seen...
January 13, 2017: BMC Urology
https://www.readbyqxmd.com/read/28052254/pan-cancer-immunogenomic-analyses-reveal-genotype-immunophenotype-relationships-and-predictors-of-response-to-checkpoint-blockade
#15
Pornpimol Charoentong, Francesca Finotello, Mihaela Angelova, Clemens Mayer, Mirjana Efremova, Dietmar Rieder, Hubert Hackl, Zlatko Trajanoski
The Cancer Genome Atlas revealed the genomic landscapes of human cancers. In parallel, immunotherapy is transforming the treatment of advanced cancers. Unfortunately, the majority of patients do not respond to immunotherapy, making the identification of predictive markers and the mechanisms of resistance an area of intense research. To increase our understanding of tumor-immune cell interactions, we characterized the intratumoral immune landscapes and the cancer antigenomes from 20 solid cancers and created The Cancer Immunome Atlas (https://tcia...
January 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28031719/potential-role-of-immunotherapy-in-advanced-non-small-cell-lung-cancer
#16
REVIEW
Ramon Andrade de Mello, Ana Flávia Veloso, Paulo Esrom Catarina, Sara Nadine, Georgios Antoniou
Immuno checkpoint inhibitors have ushered in a new era with respect to the treatment of advanced non-small-cell lung cancer. Many patients are not suitable for treatment with epidermal growth factor receptor tyrosine kinase inhibitors (eg, gefitinib, erlotinib, and afatinib) or with anaplastic lymphoma kinase inhibitors (eg, crizotinib and ceritinib). As a result, anti-PD-1/PD-L1 and CTLA-4 inhibitors may play a novel role in the improvement of outcomes in a metastatic setting. The regulation of immune surveillance, immunoediting, and immunoescape mechanisms may play an interesting role in this regard either alone or in combination with current drugs...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28018344/adjunct-strategies-for-tuberculosis-vaccines-modulating-key-immune-cell-regulatory-mechanisms-to-potentiate-vaccination
#17
REVIEW
Lakshmi Jayashankar, Richard Hafner
Tuberculosis (TB) remains a global health threat of alarming proportions, resulting in 1.5 million deaths worldwide. The only available licensed vaccine, Bacillus Calmette-Guérin, does not confer lifelong protection against active TB. To date, development of an effective vaccine against TB has proven to be elusive, and devising newer approaches for improved vaccination outcomes is an essential goal. Insights gained over the last several years have revealed multiple mechanisms of immune manipulation by Mycobacterium tuberculosis (Mtb) in infected macrophages and dendritic cells that support disease progression and block development of protective immunity...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/28006927/the-safety-of-therapeutic-monoclonal-antibodies-implications-for-cancer-therapy-including-immuno-checkpoint-inhibitors
#18
R Demlova, D Valík, R Obermannova, L ZdraŽilová-Dubská
Monoclonal antibody-based treatment of cancer has been established as one of the most successful therapeutic strategies for both hematologic malignancies and solid tumors. In addition to targeting cancer antigens antibodies can also modulate immunological pathways that are critical to immune surveillance. Antibody therapy directed against several negative immunologic regulators (checkpoints) is demonstrating significant success in the past few years. Immune checkpoint inhibitors, ipilimumab, pembrolizumab and nivolumab, have shown significant clinical benefit in several malignancies and are already approved for advanced melanoma and squamous NSCLC...
December 21, 2016: Physiological Research
https://www.readbyqxmd.com/read/27960591/immuno-oncology-for-renal-cell-carcinoma-treatment-future-perspectives-for-combinations-and-sequences-with-molecularly-targeted-agents
#19
Camillo Porta, Ilaria Toscani, Anna M Czarnecka, Cezary A Szczylik
From a theoretical viewpoint, combining molecularly targeted agents endowed with antiangiogenic properties with immunotherapy makes sense in treatment of metastatic renal cell carcinoma (RCC); this neoplasm is highly angiogenesis-dependent, as well as potentially immunogenic. Areas covered: The authors performed a literature search looking for clinical trials aimed at evaluating efficacy and tolerability of combinations (or sequences) of molecularly targeted agents and different immunotherapeutic approaches in metastatic RCC...
February 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/27941289/immune-checkpoint-inhibitors-in-hematologic-malignancies
#20
Dai Maruyama
Immuno-checkpoint inhibitors are one of the most promising immunotherapies for various advanced cancers including hematologic malignancies. Recently, enhanced signaling of the PD-1/CTLA4 pathway has emerged as a critical mechanism by which tumors can escape the anti-tumor immune response. PD-1-blocking antibodies have been used to enhance immunity in several malignancies and obtain durable responses, especially in patients with heavily treated relapsed/refractory Hodgkin lymphoma. Currently, several clinical trials including single agent or combination therapies for hematologic malignancies, such as Hodgkin lymphoma, B-cell lymphomas and multiple myeloma, are ongoing...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
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