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Immuno oncology

Seung Sook Paik, In Kyoung Hwang, Myung Jae Park, Seung Hyeun Lee
BACKGROUND: Although targeted therapy and immuno-oncology have shifted the treatment paradigm for lung cancer, platinum-based combination is still the standard of care for advanced non-small cell lung cancer (NSCLC). Pemetrexed continuation maintenance therapy has been approved and increasingly used for patients with nonsquamous NSCLC. However, the efficacy of this strategy has not been proven in patients without driving mutations. The objective of this study was to compare the clinical benefit of pemetrexed continuation maintenance to conventional platinum-based doublet in epidermal growth factor receptor (EGFR)-negative lung adenocarcinoma...
March 7, 2018: Tuberculosis and Respiratory Diseases
Ariel E Marciscano, Ravi A Madan
Bacillus Calmette-Guérin in urothelial carcinoma, high-dose interleukin-2 in renal cell carcinoma, and sipuleucel-T in prostate cancer serve as enduring examples that the host immune response can be harnessed to promote effective anti-tumor immunity in genitourinary malignancies. Recently, cancer immunotherapy with immune checkpoint inhibitors has transformed the prognostic landscape leading to durable responses in a subset of urothelial carcinoma and renal cell carcinoma patients with traditionally poor prognosis...
March 8, 2018: Current Treatment Options in Oncology
Stephanie C Casey, Virginie Baylot, Dean W Felsher
The MYC proto-oncogene is a gene product that coordinates the transcriptional regulation of a multitude of genes that are essential to cellular programs required for normal as well as neoplastic cellular growth and proliferation, including cell cycle, self-renewal, survival, cell growth, metabolism, protein and ribosomal biogenesis, and differentiation. Here we propose that MYC regulates these programs in a manner that is coordinated with a global influence on the host immune response. MYC had been presumed to contribute to tumorigenesis through tumor cell intrinsic influences...
March 7, 2018: Blood
Keith E Steele, Tze Heng Tan, René Korn, Karma Dacosta, Charles Brown, Michael Kuziora, Johannes Zimmermann, Brian Laffin, Moritz Widmaier, Lorenz Rognoni, Ruben Cardenes, Katrin Schneider, Anmarie Boutrin, Philip Martin, Jiping Zha, Tobias Wiestler
BACKGROUND: Immuno-oncology and cancer immunotherapies are areas of intense research. The numbers and locations of CD8+ tumor-infiltrating lymphocytes (TILs) are important measures of the immune response to cancer with prognostic, pharmacodynamic, and predictive potential. We describe the development, validation, and application of advanced image analysis methods to characterize multiple immunohistochemistry-derived CD8 parameters in clinical and nonclinical tumor tissues. METHODS: Commercial resection tumors from nine cancer types, and paired screening/on-drug biopsies of non-small-cell lung carcinoma (NSCLC) patients enrolled in a phase 1/2 clinical trial investigating the PD-L1 antibody therapy durvalumab (NCT01693562), were immunostained for CD8...
March 6, 2018: Journal for Immunotherapy of Cancer
Aman Chauhan, Millicent Horn, Gray Magee, Kurt Hodges, Mark Evers, Susanne Arnold, Lowell Anthony
This unique case series and review of literature suggests that immune checkpoint inhibitors may have clinical activity in neuroendocrine tumors. Objective: Summarize advances of immuno-oncology in neuroendocrine tumors with the help of a case series. Design: Case series and review of literature. Intervention or Exposure: The patients were treated with immune checkpoint inhibitors (pembrolizumab or nivolumab). Main Outcomes and Measuress: Life expectancy, quality of life, disease progression...
February 6, 2018: Oncotarget
Yuri Kosinsky, Simon J Dovedi, Kirill Peskov, Veronika Voronova, Lulu Chu, Helen Tomkinson, Nidal Al-Huniti, Donald R Stanski, Gabriel Helmlinger
BACKGROUND: Numerous oncology combination therapies involving modulators of the cancer immune cycle are being developed, yet quantitative simulation models predictive of outcome are lacking. We here present a model-based analysis of tumor size dynamics and immune markers, which integrates experimental data from multiple studies and provides a validated simulation framework predictive of biomarkers and anti-tumor response rates, for untested dosing sequences and schedules of combined radiation (RT) and anti PD-(L)1 therapies...
February 27, 2018: Journal for Immunotherapy of Cancer
Kristine A Frerichs, Noemi Anna Nagy, Pieter L Lindenbergh, Patty Bosman, Jhon Marin Soto, Marloes Broekmans, Richard W J Groen, Maria Themeli, Louise Nieuwenhuis, Claudia Stege, Inger S Nijhof, Tuna Mutis, Sonja Zweegman, Henk M Lokhorst, Niels W C J van de Donk
Multiple myeloma (MM) is generally an incurable hematological malignancy with heterogeneous overall survival rates ranging from a few months to more than 10 years. Survival is especially poor for patients who developed disease that is refractory to immunomodulatory drugs and proteasome inhibitors. Areas covered: This review will discuss the importance of CD38-targeting antibodies for the treatment of MM patients to improve their outcome. Expert commentary: Intense immuno-oncological laboratory research has resulted in the development of functionally active monoclonal antibodies against cell surface markers present on MM cells...
March 2018: Expert Review of Clinical Immunology
Natalie J Rothenberger, Ashwin Somasundaram, Laura P Stabile
Estrogen receptors are broadly expressed in many cell types involved in the innate and adaptive immune responses, and differentially regulate the production of cytokines. While both genomic and non-genomic tumor cell promoting mechanisms of estrogen signaling are well characterized in multiple carcinomas including breast, ovarian, and lung, recent investigations have identified a potential immune regulatory role of estrogens in the tumor microenvironment. Tumor immune tolerance is a well-established mediator of oncogenesis, with increasing evidence indicating the importance of the immune response in tumor progression...
February 19, 2018: International Journal of Molecular Sciences
P J Schuler, A von Witzleben, J Doescher, B Wollenberg, A Dietz, T K Hoffmann
In recent years, immunotherapy has been shown to be a promising approach for the treatment of various tumor entities. Due to further pharmacological developments and new studies, the checkpoint inhibitors have now arrived in the clinic. To date, patients with cancers in the head and neck region have benefited from these agents as part of a palliative therapy. Current clinical trials are testing other indications for the checkpoint inhibitors as monotherapy or in combination with other therapeutic approaches...
February 19, 2018: HNO
B Allard, S Aspeslagh, S Garaud, F A Dupont, C Solinas, M Kok, B Routy, C Sotiriou, J Stagg, L Buisseret
Cancer immunotherapy is demonstrating impressive clinical benefit in different malignancies and clinical oncologists are increasingly turning their attention to immune-oncology. It is now well recognized that innate and adaptive immune cells infiltrating tumors are associated with clinical outcomes and responses to treatments, and can be harnessed to patients' benefit. Considerable advances have also been made in understanding how cancers escape from immune attack. Targeting of immunological escape processes regulated by the expression of immune checkpoint receptors and ligands and the down-modulation of tumor antigen presentation is the basis of immuno-oncology treatments...
February 8, 2018: Seminars in Cancer Biology
Hideo Kunitoh
No abstract text is available yet for this article.
February 1, 2018: Japanese Journal of Clinical Oncology
Danuta J Herzyk, Helen G Haggerty
The development of novel therapies that can harnass the immune system to eradicate cancer is an area of intensive research. Several new biopharmaceuticals that target the immune system rather than the tumor itself have recently been approved and fundamentally transformed treatment of many cancer diseases. This success has intensified the search for new targets and modalities that could be developed as even more effective therapeutic agents either as monotherapy or in combination. While great benefits of novel immunotherapies in oncology are evident, the safety of these therapies has to also be addressed as their desired pharmacology, immune activation, can lead to "exaggerated" effects and toxicity...
February 7, 2018: AAPS Journal
Nacer Abrouk, Bryan Oronsky, Scott Caroen, Shoucheng Ning, Susan Knox, Donna Peehl
Responses to immuno-oncology agents are often subject to misinterpretation as apparent tumor growth due to immune infiltration leads to the appearance of progressive disease and can result in the discontinuation of effective therapeutic agents. Better statistical strategies to determine experimental outcomes are needed to distinguish between true and pseudoprogression. We applied time-to-event statistical analyses methods that account for study design features and capture the longitudinal and panoramic aspects of pseudoprogression to test superiority of a combination of RRx-001, a novel tumor-associated macrophage polarizing agent in Phase 2, and an anti-PD-L1 antibody in a myeloma preclinical model, comparing to traditional, mean-based mixed effects modeling approaches that did not show statistical significance...
February 5, 2018: Cancer Chemotherapy and Pharmacology
Alessandra Cesano, Sarah Warren
The recent successes in the use of immunotherapy to treat cancer have led to a multiplicity of new compounds in development. Novel clinical-grade biomarkers are needed to guide the choice of these agents to obtain the maximal likelihood of patient benefit. Predictive biomarkers for immunotherapy differ from the traditional biomarkers used for targeted therapies: the complexity of the immune response and tumour biology requires a more holistic approach than the use of a single analyte biomarker. This paper reviews novel biomarker approaches for the effective development of immune-oncology therapies, highlighting the promise of the advances in next-generation gene expression profiling that allow biologic information to be efficiently organized and interpreted for a maximum predictive value at the individual patient level...
February 2, 2018: Biomedicines
Yan Ji, Jin Y Jin, David M Hyman, Geoffrey Kim, Ajit Suri
No abstract text is available yet for this article.
February 1, 2018: Clinical and Translational Science
H R Shwetha, T Smitha
No abstract text is available yet for this article.
September 2017: Journal of Oral and Maxillofacial Pathology: JOMFP
Jiajia Zhang, Christopher L Wolfgang, Lei Zheng
Pancreatic cancer, most commonly referring to pancreatic ductal adenocarcinoma (PDAC), remains one of the most deadly diseases, with very few effective therapies available. Emerging as a new modality of modern cancer treatments, immunotherapy has shown promises for various cancer types. Over the past decades, the potential of immunotherapy in eliciting clinical benefits in pancreatic cancer have also been extensively explored. It has been demonstrated in preclinical studies and early phase clinical trials that cancer vaccines were effective in eliciting anti-tumor immune response, but few have led to a significant improvement in survival...
January 30, 2018: Cancers
Hélène Kaplon, Marie-Caroline Dieu-Nosjean
The role of B lymphocytes in tumor immuno-surveillance has been neglected for a long time because it has been often considered to be ineffective if not pro-tumoral. Extensive studies of the tumor immune microenvironment, particularly in humans, has now made it possible to specify the nature of the interactions between B cells and their cellular partners. This review will present a number of parameters that dictate the fate of B cells toward a pro-tumor versus an anti-tumor function. Thus, the ability to elicit a B cell-and/or an antibody-dependent anti-tumor immunity involves a wide variety of molecular and cellular mechanisms, some of which may represent novel therapeutic targets in oncology...
January 2018: Médecine Sciences: M/S
Ariel E Marciscano, Joshua M Walker, Heather M McGee, Michelle M Kim, Charles A Kunos, Arta M Monjazeb, Stephen L Shiao, Phuoc T Tran, Mansoor M Ahmed
Radiotherapy (RT) has been a fundamental component of the anti-cancer armamentarium for over a century. Approximately half of all cancer patients are treated with radiotherapy during their disease course. Over the two past decades, there has been a growing body of preclinical evidence supporting the immunomodulatory effects of radiotherapy, particularly when combined with immunotherapy, but only anecdotal clinical examples existed until recently. The renaissance of immunotherapy and the recent U.S. Food and Drug Administration (FDA) approval of several immune checkpoint inhibitors (ICIs) and other immuno-oncology (IO) agents in multiple cancers provides the opportunity to investigate how localized radiotherapy can induce systemic immune responses...
January 29, 2018: Journal for Immunotherapy of Cancer
Adamu Abdullahi, Muhammad Inuwa Mustapha, Dawotola Ayorinde David, Olasinde Tajudeen Ayodeji
BACKGROUND: Cervical cancer is the commonest gynecological malignancy in our environment and is an Acquired Immuno-Deficiency Syndrome (AIDS)-associated malignancy. Documented data on the Human Immune-deficiency Virus (HIV) seroprevalence among patients with cervical cancer in our environment are scarce. OBJECTIVE: The aim of this study is to determine the prevalence of HIV infection in women with cancer of the cervix. STUDY DESIGN: The work is a descriptive survey by design, concentrating in frequency of occurrences of prevalence of the dissease in either cases for a number of years retrospectively carried out at the Radiotherapy and Oncology Centre of Ahmadu Bello University Teaching Hospital (ABUTH) Zaria...
January 2018: Annals of African Medicine
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