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https://www.readbyqxmd.com/read/28201977/targeting-the-immune-niche-within-the-bone-marrow-microenvironment-the-rise-of-immunotherapy-in-multiple-myeloma
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/27941285/basics-of-cancer-immunotherapy
#13
Yuki Fujioka, Hiroyoshi Nishikawa
The immune system is the body's defense against infectious organisms and other invaders including cancer cells. Cancer immunotherapy, which employs our own immune systems to attack cancer cells, is now emerging as a promising modality of cancer treatment based upon the clinical successes of immune checkpoint blockade and adoptive T cell transfer. In hematologic malignancies, clinical application of anti-PD-1 mAb and CAR (chimeric antigen receptor) T therapy is now being extensively tested in Hodgkin's disease, multiple myeloma, and CD19(+) acute lymphocytic leukemia...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/27936870/emerging-biomarkers-for-pd-1-pathway-cancer-therapy
#14
Joline Sj Lim, Raghav Sundar, Maxime Chénard-Poirier, Juanita Lopez, Timothy A Yap
The field of immuno-oncology has witnessed unprecedented success in recent years, with several PD=1 and PD-L1 inhibitors obtaining US FDA registration and breakthrough drug therapy designation in multiple tumor types. Despite its clear efficacy in certain cancers, treatment with these agents carries a risk of immune-related toxicities and substantial financial burden. It is, therefore, critical to identify patients likely to benefit from such immunotherapies and develop strategies to differentiate responders from nonresponders early during treatment...
January 2017: Biomarkers in Medicine
https://www.readbyqxmd.com/read/27931845/immuno-oncology-allying-forces-of-radio-and-immuno-therapy-to-enhance-cancer-cell-killing
#15
REVIEW
Jacques Bernier
Besides the local effects of ionizing radiation at the cellular and molecular levels in tumor tissues, the interactions of radiotherapy with the host's immune system are nowadays at the center of many investigations. In some cases, these interactions can be strong enough to immunize the patient against the tumor, leading to a rejection by the host of both the irradiated tumor and distant metastases. In this latter case, the rejection mechanism is called "abscopal effect". Over the last two decades, increasing attention has also been paid to the combination of various forms of immunotherapies with radiation, as an attempt to boost cancer cell killing mechanisms...
December 2016: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/27930550/role-of-immune-cells-in-pancreatic-cancer-from-bench-to-clinical-application-an-updated-review
#16
REVIEW
Jae Hyuck Chang, Yongjian Jiang, Venu G Pillarisetty
BACKGROUND: Pancreatic cancer (PC) remains difficult to treat, despite the recent advances in various anticancer therapies. Immuno-inflammatory response is considered to be a major risk factor for the development of PC in addition to a combination of genetic background and environmental factors. Although patients with PC exhibit evidence of systemic immune dysfunction, the PC microenvironment is replete with immune cells. METHODS: We searched PubMed for all relevant English language articles published up to March 2016...
December 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27923825/rational-selection-of-syngeneic-preclinical-tumor-models-for-immunotherapeutic-drug-discovery
#17
Suzanne I S Mosely, John E Prime, Richard C A Sainson, Jens-Oliver Koopmann, Dennis Y Q Wang, Danielle M Greenawalt, Miika J Ahdesmaki, Rebecca Leyland, Stefanie Mullins, Luciano Pacelli, Danielle Marcus, Judith Anderton, Amanda Watkins, Jane Coates Ulrichsen, Philip Brohawn, Brandon W Higgs, Matthew McCourt, Hazel Jones, James A Harper, Michelle Morrow, Viia Valge-Archer, Ross Stewart, Simon J Dovedi, Robert W Wilkinson
Murine syngeneic tumor models are critical to novel immuno-based therapy development, but the molecular and immunologic features of these models are still not clearly defined. The translational relevance of differences between the models is not fully understood, impeding appropriate preclinical model selection for target validation, and ultimately hindering drug development. Across a panel of commonly used murine syngeneic tumor models, we showed variable responsiveness to immunotherapies. We used array comparative genomic hybridization, whole-exome sequencing, exon microarray analysis, and flow cytometry to extensively characterize these models, which revealed striking differences that may underlie these contrasting response profiles...
December 6, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27846884/future-perspectives-in-melanoma-research-meeting-report-from-the-melanoma-bridge-napoli-december-1st-4th-2015
#18
Paolo A Ascierto, Sanjiv Agarwala, Gerardo Botti, Alessandra Cesano, Gennaro Ciliberto, Michael A Davies, Sandra Demaria, Reinhard Dummer, Alexander M Eggermont, Soldano Ferrone, Yang Xin Fu, Thomas F Gajewski, Claus Garbe, Veronica Huber, Samir Khleif, Michael Krauthammer, Roger S Lo, Giuseppe Masucci, Giuseppe Palmieri, Michael Postow, Igor Puzanov, Ann Silk, Stefani Spranger, David F Stroncek, Ahmad Tarhini, Janis M Taube, Alessandro Testori, Ena Wang, Jennifer A Wargo, Cassian Yee, Hassane Zarour, Laurence Zitvogel, Bernard A Fox, Nicola Mozzillo, Francesco M Marincola, Magdalena Thurin
The sixth "Melanoma Bridge Meeting" took place in Naples, Italy, December 1st-4th, 2015. The four sessions at this meeting were focused on: (1) molecular and immune advances; (2) combination therapies; (3) news in immunotherapy; and 4) tumor microenvironment and biomarkers. Recent advances in tumor biology and immunology has led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS) of cancer patients. Immunotherapies in particular have emerged as highly successful approaches to treat patients with cancer including melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), bladder cancer, and Hodgkin's disease...
November 15, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27792052/novel-insights-in-the-regulation-and-function-of-macrophages-in-the-tumor-microenvironment
#19
Evangelia Bolli, Kiavash Movahedi, Damya Laoui, Jo A Van Ginderachter
PURPOSE OF REVIEW: Tumors contain not only cancer cells but also nontransformed types of cells, the stromal cells. A bidirectional interplay exists between transformed and nontransformed cells leading to tumor progression and metastasis. Tumor-associated macrophages (TAMs) are the most abundant tumor-infiltrating leukocytes characterized by a high heterogeneity and plasticity. TAMs exhibit strong protumoral activities and are related to bad prognosis and worse overall survival in various cancer types...
January 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/27789023/the-evolution-of-oncology-companion-diagnostics-from-signal-transduction-to-immuno-oncology
#20
REVIEW
Nicholas C Dracopoli, Mark S Boguski
Sixteen oncology drugs have been approved with a companion diagnostic (CDx) test by the FDA. These represent only 9.6% of the 167 oncology drug approvals since 1998, the year the first CDx test for Herceptin was approved. The great majority of CDx tests are for drugs that inhibit signal transduction pathways by either inhibiting the intracellular kinase activity with a small molecule or preventing ligand-induced receptor activation with a monoclonal antibody. In most of these cases, prospective patient selection for the biomarker-positive subpopulation was initiated in or before Phase II...
January 2017: Trends in Pharmacological Sciences
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