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Cancer and immune checkpoint

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https://www.readbyqxmd.com/read/28334399/association-of-hiv-status-with-local-immune-response-to-anal-squamous-cell-carcinoma-implications-for-immunotherapy
#1
Elizabeth L Yanik, Genevieve J Kaunitz, Tricia R Cottrell, Farah Succaria, Tracee L McMiller, Maria L Ascierto, Jessica Esandrio, Haiying Xu, Aleksandra Ogurtsova, Toby Cornish, Evan J Lipson, Suzanne L Topalian, Eric A Engels, Janis M Taube
Importance: The programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) pathway play an important immunosuppressive role in cancer and chronic viral infection, and have been effectively targeted in cancer therapy. Anal squamous cell carcinoma (SCC) is associated with both human papillomavirus and HIV infection. To date, patients with HIV have been excluded from most trials of immune checkpoint blocking agents, such as anti-PD-1 and anti-PD-L1, because it was assumed that their antitumor immunity was compromised compared with immunocompetent patients...
March 23, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28331614/sudden-hearing-loss-in-a-melanoma-patient-on-pembrolizumab-an-etiology-not-to-be-omitted-in-the-differential-diagnosis
#2
EDITORIAL
Marc-Elie Nader, Jeffrey N Myers, Paul W Gidley
Immune checkpoint inhibitors have emerged as a promising therapeutic option for metastatic cancers. However, they have been associated with inflammatory adverse reactions in various organ systems. A recent article reported a case of sudden bilateral hearing loss that occurred in a patient with metastatic melanoma being treated with pembrolizumab. The authors attributed that complication to an autoimmune reaction secondary to the treatment. This commentary discusses the importance of considering the diagnosis of leptomeningeal metastasis in patients with metastatic melanoma who present with new cranial nerve deficits...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28331342/spotlight-on-atezolizumab-and-its-potential-in-the-treatment-of-advanced-urothelial-bladder-cancer
#3
REVIEW
Ahmet Murat Aydin, Solomon L Woldu, Ryan C Hutchinson, Martin Boegemann, Aditya Bagrodia, Yair Lotan, Vitaly Margulis, Laura-Maria Krabbe
Metastatic urothelial carcinoma of the bladder is an aggressive malignancy with poor prognosis, reflecting a lack of effective systemic therapies. The current standard of care includes multiagent platinum-based chemotherapy; however a majority of patients do not respond to treatment and most eventually succumb to disease. Recently, renewed interest in immunotherapy in the form of immune-checkpoint inhibition has gained widespread attention for a number of malignancies. Atezolizumab, an anti-PDL1 antibody, has been shown to be effective in a subset of patients previously treated with or unfit for platinum-based chemotherapy, and has shown durable responses with a good tolerability profile...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28328001/cancer-vaccines-at-the-age-of-immune-checkpoint-inhibitors-reasonable-approach-as-combination-therapy-in-advanced-urothelial-carcinoma
#4
Petros Grivas, Vadim S Koshkin, Sumanta K Pal
No abstract text is available yet for this article.
February 21, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28325288/retroviral-replicating-vector-delivery-of-mir-pdl1-inhibits-immune-checkpoint-pdl1-and-enhances-immune-responses-in%C3%A2-vitro
#5
Amy H Lin, Christopher G Twitty, Ryan Burnett, Andrew Hofacre, Leah A Mitchell, Fernando Lopez Espinoza, Harry E Gruber, Douglas J Jolly
Tumor cells express a number of immunosuppressive molecules that can suppress anti-tumor immune responses. Efficient delivery of small interfering RNAs to treat a wide range of diseases including cancers remains a challenge. Retroviral replicating vectors (RRV) can be used to stably and selectively introduce genetic material into cancer cells. Here, we designed RRV to express shRNA (RRV-shPDL1) or microRNA30-derived shRNA (RRV-miRPDL1) using Pol II or Pol III promoters to downregulate PDL1 in human cancer cells...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28325210/breast-cancer-immunology-and-immunotherapy-current-status-and-future-perspectives
#6
L de la Cruz-Merino, M Chiesa, R Caballero, F Rojo, N Palazón, F H Carrasco, V Sánchez-Margalet
Cancer immunology has gained renewed interest in the past few years due to emerging findings on mechanisms involved in tumoral immune evasion. Indisputably, immune edition is currently considered a critical hallmark of cancer. Basic research has revealed new targets which can be modulated in the clinical setting with new compounds and strategies. As recent evidence confirms, breast cancer (BC) is a complex and heterogeneous disease in which host immune responses play a substantial role. T-infiltrating lymphocytes measurement is suggested as a powerful new tool necessary to predict early BC evolution, especially in HER2-positive and triple negative subtypes...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28324750/biological-mechanisms-of-immune-escape-and-implications-for-immunotherapy-in-head-and-neck-squamous-cell-carcinoma
#7
REVIEW
Jennifer D Moy, Jessica M Moskovitz, Robert L Ferris
Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with high morbidity and mortality. Despite advances in cytotoxic therapies and surgical techniques, overall survival (OS) has not improved over the past few decades. This emphasises the need for intense investigation into novel therapies with good tumour control and minimal toxicity. Cancer immunotherapy has led this endeavour, attempting to improve tumour recognition and expand immune responses against tumour cells. While various forms of HNSCC immunotherapy are in preclinical trials, the most promising direction thus far has been with monoclonal antibodies (mAbs), targeting growth factor and immune checkpoint receptors...
March 18, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28323658/changing-face-of-metastatic-prostate-cancer-the-law-of-diminishing-returns-holds-true
#8
Ulka N Vaishampayan
PURPOSE OF REVIEW: Prostate cancer presents with a multitude of faces. It ranges from localized cancers staying quiescent for many years during active surveillance to the raging diffuse liver metastases causing terminal disease. The incidence of metastatic disease is increasing. This review will highlight some of the recent developments as well as ongoing challenges of managing advanced prostate cancer. RECENT FINDINGS: Significant strides are being made in managing metastatic prostate cancer...
March 18, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28323141/mechanistic-and-pharmacologic-insights-on-immune-checkpoint-inhibitors
#9
REVIEW
Randy F Sweis, Jason J Luke
The concept of augmenting the immune system to eradicate cancer dates back at least a century. A major resurgence in cancer immunotherapy has occurred over the past decade since the identification and targeting of negative regulators with antibody therapies to augment the anti-tumor immune response. Unprecedented responses across a broad array of cancer types elevated this class of therapies to the forefront of cancer treatment. The most successful drugs to date target the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) pathways...
March 18, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28322974/current-modalities-in-cancer-immunotherapy-immunomodulatory-antibodies-cars-and-vaccines
#10
REVIEW
Jason Lohmueller, Olivera J Finn
Successes of immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) T cell therapy in curing patients with otherwise lethal cancers have validated immunotherapy as a treatment for cancer and have inspired excitement for its broader potential. Most promising is the ability of each approach to eliminate bulky and advanced-stage cancers and to achieve durable cures. Despite this success, to date only a subset of cancer patients and a limited number of cancer types respond to these therapies. A major goal now is to expand the types of cancer and number of patients who can be successfully treated...
March 16, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28321817/adverse-events-in-cancer-immunotherapy
#11
Noha Abdel-Wahab, Anas Alshawa, Maria E Suarez-Almazor
Cancer immunotherapy has resulted in durable responses in patients with metastatic disease, unseen with traditional chemotherapy. Several therapies have been approved by the Food and Drug Administration for the treatment of various cancers, including: immune checkpoint inhibitors, cytokines - interleukin 2 (IL-2) and interferon alpha (IFN), and the cancer vaccine sipuleucel-T. These therapies upregulate the immune system to enhance antitumor responses. As a consequence, they can cause inflammatory and immune-related adverse events that can affect one or more organs, can be serious, and on occasion lifethreatening...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28321130/effective-combinatorial-immunotherapy-for-castration-resistant-prostate-cancer
#12
Xin Lu, James W Horner, Erin Paul, Xiaoying Shang, Patricia Troncoso, Pingna Deng, Shan Jiang, Qing Chang, Denise J Spring, Padmanee Sharma, John A Zebala, Dean Y Maeda, Y Alan Wang, Ronald A DePinho
A significant fraction of patients with advanced prostate cancer treated with androgen deprivation therapy experience relapse with relentless progression to lethal metastatic castration-resistant prostate cancer (mCRPC). Immune checkpoint blockade using antibodies against cytotoxic-T-lymphocyte-associated protein 4 (CTLA4) or programmed cell death 1/programmed cell death 1 ligand 1 (PD1/PD-L1) generates durable therapeutic responses in a significant subset of patients across a variety of cancer types. However, mCRPC showed overwhelming de novo resistance to immune checkpoint blockade, motivating a search for targeted therapies that overcome this resistance...
March 20, 2017: Nature
https://www.readbyqxmd.com/read/28319731/stimulating-cd27-to-quantitatively-and-qualitatively-shape-adaptive-immunity-to-cancer
#13
REVIEW
Timothy Nj Bullock
The capacity of the immune system to recognize and respond to tumors has been appreciated for over 100 years. However, clinical success has largely depended on the elucidation of the positive and negative regulators of effector cells after their activation via the antigen cell receptor. On the one hand, effector cells upregulate checkpoint molecules that are thought to play a role in limiting immunopathology. On the other, second and third waves of costimulation are often required to promote the expansion, survival and differentiation of effector cells...
March 16, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28318336/are-tumor-infiltrating-lymphocytes-protagonists-or-background-actors-in-patient-selection-for-cancer-immunotherapy
#14
Federica Zito Marino, Paolo Antonio Ascierto, Giulio Rossi, Stefania Staibano, Marco Montella, Daniela Russo, Roberto Alfano, Alessandro Morabito, Gerardo Botti, Renato Franco
Tumor-infiltrating lymphocytes (TILs) are frequently observed in several tumors, reflecting the dynamic process of ''cancer immunoediting''. Prognostic and predictive values of TILs have been demonstrated in different cancers, proving their pivotal role in clinical outcome. In recent years, new therapies targeting immune checkpoint inhibitors, especially CTLA-4 and PD-1/PDL-1 pathways, have been introduced into clinical practice. In this context, TILs may even have a possible utility as a predictive biomarker for immunotherapy response...
March 20, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28317871/insights-into-molecular-therapy-of-glioma-current-challenges-and-next-generation-blueprint
#15
REVIEW
Y Rajesh, Ipsita Pal, Payel Banik, Sandipan Chakraborty, Sachin A Borkar, Goutam Dey, Ahona Mukherjee, Mahitosh Mandal
Glioma accounts for the majority of human brain tumors. With prevailing treatment regimens, the patients have poor survival rates. In spite of current development in mainstream glioma therapy, a cure for glioma appears to be out of reach. The infiltrative nature of glioma and acquired resistance substancially restrict the therapeutic options. Better elucidation of the complicated pathobiology of glioma and proteogenomic characterization might eventually open novel avenues for the design of more sophisticated and effective combination regimens...
March 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28315555/checkpoint-inhibitors-common-immune-related-adverse-events-and-their-management%C3%A2
#16
RuthAnn Gordon, Mary Kate Kasler, Kristen Stasi, Yelena Shames, Mimma Errante, Kathryn Ciccolini, Anna Skripnik Lucas, Pam Raasch, Erica Fischer-Cartlidge
BACKGROUND: Immunotherapy, specifically the use of checkpoint inhibitors, offers patients with cancer an alternative to chemotherapy, targeting different pathways to destroy cancer cells. The side effects of immunotherapies, as well as their impact on normal tissue, need to be assessed and managed based on their mechanisms of action. OBJECTIVES: This article presents an overview of immune-related adverse events (AEs). 
. METHODS: Common immune-related toxicities, as well as rare and refractory toxicities, are reviewed...
April 1, 2017: Clinical Journal of Oncology Nursing
https://www.readbyqxmd.com/read/28315552/cancer-immunotherapy-an-evidence-based-overview-and-implications-for-practice
#17
Virginia Bayer, Beau Amaya, Diane Baniewicz, Colleen Callahan, Lisa Marsh, Asia S McCoy
BACKGROUND: Significant research progress has been made in immunotherapies since the mid-1990s, and this rapid evolution necessitates evidence-based education on immunotherapies, their pathophysiology, and their toxicities to provide safe, effective care.
. OBJECTIVES: The aim of this article is to provide an evidence-based overview, with implications for practice, of checkpoint inhibitors, monoclonal antibodies, oncolytic viral therapies, and chimeric antigen receptor T-cell therapies...
April 1, 2017: Clinical Journal of Oncology Nursing
https://www.readbyqxmd.com/read/28315541/hypophysitis-nursing-management-of-immune-related-adverse-events%C3%A2
#18
Adrienne Vazquez
Immunotherapy can treat cancer and prevent future cancer relapse by enhancing the body's immune system. With novel immunotherapeutic agents like checkpoint inhibitors come unique immune-related adverse events. Hypophysitis, one of the lesser known immune-related complications, may be observed in patients receiving checkpoint inhibitors. Although the acute symptoms of immune-related hypophysitis may be managed with attentive monitoring and high-dose corticosteroids, lifelong hormone substitution therapy may be warranted...
April 1, 2017: Clinical Journal of Oncology Nursing
https://www.readbyqxmd.com/read/28315206/otorhinolaryngological-toxicities-of-new-drugs-in-oncology
#19
REVIEW
Dana M Hartl, Daphné Morel, Erika Saavedra, Christophe Massard, Alessandra Rinaldo, Nabil F Saba, Alfio Ferlito, Jean-Charles Soria
Many new or relatively new cancer drugs-personalized anticancer agents-have been approved for use in various clinical settings in oncology or are still under evaluation in clinical trials. Targeted therapies as well as new immune checkpoint blockers have toxicity profiles that differ from conventional cytotoxic chemotherapy, and many can cause adverse effects that affect the mouth and pharynx, the nasal cavities, and the larynx. This review aims to provide an overview of current knowledge concerning these side effects and contemporary management...
March 17, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28315073/mechanisms-of-resistance-to-immune-checkpoint-antibodies
#20
Rodrigo N Ramos, Eliane Piaggio, Emanuela Romano
Immunotherapy using checkpoint inhibitors has changed the way we treat several aggressive cancers such as melanoma, non-small cell lung and head & neck cancers, among others, with durable responses achieved in the metastatic setting. However, unfortunately, the vast majority of patients do not respond to checkpoint inhibition therapy and a minority of patients, who do respond to treatment, develop secondary resistance and experience relapse by mechanisms still inadequately understood. Emerging evidence shows that alterations in multiple signaling pathways are involved in primary and/or secondary resistance to checkpoint inhibition...
March 18, 2017: Handbook of Experimental Pharmacology
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