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Immune programming

Kelly D Moynihan, Cary F Opel, Gregory L Szeto, Alice Tzeng, Eric F Zhu, Jesse M Engreitz, Robert T Williams, Kavya Rakhra, Michael H Zhang, Adrienne M Rothschilds, Sudha Kumari, Ryan L Kelly, Byron H Kwan, Wuhbet Abraham, Kevin Hu, Naveen K Mehta, Monique J Kauke, Heikyung Suh, Jennifer R Cochran, Douglas A Lauffenburger, K Dane Wittrup, Darrell J Irvine
Checkpoint blockade with antibodies specific for cytotoxic T lymphocyte-associated protein (CTLA)-4 or programmed cell death 1 (PDCD1; also known as PD-1) elicits durable tumor regression in metastatic cancer, but these dramatic responses are confined to a minority of patients. This suboptimal outcome is probably due in part to the complex network of immunosuppressive pathways present in advanced tumors, which are unlikely to be overcome by intervention at a single signaling checkpoint. Here we describe a combination immunotherapy that recruits a variety of innate and adaptive immune cells to eliminate large tumor burdens in syngeneic tumor models and a genetically engineered mouse model of melanoma; to our knowledge tumors of this size have not previously been curable by treatments relying on endogenous immunity...
October 24, 2016: Nature Medicine
Theresa L Whiteside
Tumor-derived exosomes (TEX) are emerging as critical components of an intercellular information network between the tumor and the host. The tumor escapes from the host immune system by using a variety of mechanisms designed to impair or eliminate anti-tumor immunity. TEX carrying a cargo of immunoinhibitory molecules and factors represent one such mechanism. TEX, which are present in all body fluids of cancer patients, deliver negative molecular or genetic signals to immune cells re-programming their functions...
October 20, 2016: Vaccines
Hanna Starobinets, Jordan Ye, Miranda Broz, Kevin Barry, Juliet Goldsmith, Timothy Marsh, Fanya Rostker, Matthew Krummel, Jayanta Debnath
The rising success of cancer immunotherapy has produced immense interest in defining the clinical contexts that may benefit from this therapeutic approach. To this end, there is a need to ascertain how the therapeutic modulation of intrinsic cancer cell programs influences the anticancer immune response. For example, the role of autophagy as a tumor cell survival and metabolic fitness pathway is being therapeutically targeted in ongoing clinical trials that combine cancer therapies with antimalarial drugs for the treatment of a broad spectrum of cancers, many of which will likely benefit from immunotherapy...
October 24, 2016: Journal of Clinical Investigation
Sarikapan Wilailak, Nuttapong Lertchaipattanakul
Between the years of 2010-2012, it was estimated there were a total of 112,392 new cases of cancers in Thailand, thus, the total age-standardized rate (ASR) per 100,000 is 137.6. In regards to the most prevalent types of cancer in female, breast cancer has the highest ASR, followed by cervical cancer (ASR=14.4); liver and bile duct cancer; colon and rectum cancer; trachea, bronchus and lung cancer; ovarian cancer (ASR=6.0); thyroid cancer; non-Hodgkin lymphoma and uterine cancer (ASR=4.3). The trend of cervical cancer in Thailand is decreasing, one key factor in making this possible was the employment of dual tract strategy (Pap smear and visual inspection with acetic acid [VIA]) by the government in 2005...
November 2016: Journal of Gynecologic Oncology
Analía Rial, Florencia Ferrara, Norma Suárez, Paola Scavone, Juan Martín Marqués, José Alejandro Chabalgoity
Respiratory tract infections are among the most frequent infections in humans causing millions of deaths especially in children and the elderly. Antibiotics and vaccines are the main available tools of control, but resistant strains are continuously arising and available vaccines only account for few of many pathogens involved. Non-specific immunotherapies are an emerging alternative to induce protective immunity at the airways. Mucosally administered polyvalent bacterial lysates (PBLs) have been widely used for decades for prevention of respiratory diseases, but the bases of their proposed therapeutic effectiveness are still controversial...
October 20, 2016: Microbes and Infection
Anisur Rahman Siddique, Prem Singh, Geetali Trivedi
In 2009, India contributed to over half the global cases of poliomyelitis. Many believed that India would be the last country to be polio free. India proved them wrong and was certified polio free in 2014. In January 2016, India celebrated 5 years of being polio free. One of the major reasons behind the interruption of polio transmission in the Polio endemic states of Uttar Pradesh and Bihar was the deployment of Social Mobilization Network (SMNet). A three tiered structure, the 7300 strong SMNet is now the gold standard in public health communication...
August 7, 2016: Indian Pediatrics
Pradeep Haldar, Pankaj Agrawal
Global Polio Eradication and Endgame Strategic Plan 2013-18 calls for the ultimate withdrawal of oral polio vaccines (OPV) from all immunization programs across the world. The phased globally synchronized withdrawal would begin with type 2 serotype in 2016 through a switch from trivalent OPV (tOPV) to bivalent OPV (bOPV) and is associated with small but real risk of Vaccine Derived Polio Virus (VDPV) outbreaks. To mitigate this risk, efforts across the world, including India, are underway that comprise of Inactivated Polio Vaccine (IPV) introduction, containment of type 2 wild and vaccine strains, securing bOPV supplies, and surveillance and response protocols for any outbreaks after switch...
August 7, 2016: Indian Pediatrics
Khitam Muhsen, Eias Kassem, Uri Rubenstein, Sophy Goren, Moshe Ephros, Dani Cohen, Lester M Shulman
BACKGROUND: Uncertainty exists about the sustainability of the reduction in rotavirus gastroenteritis (RVGE) following the introduction of rotavirus vaccines into national immunization programs, and on its potential impact on circulating genotypes. RotaTeq was introduced into the Israeli national immunization program in December 2010, and vaccination coverage is around 80%. AIMS: To examine the change in incidence of RVGE hospitalization and rotavirus genotypes, during the five years after introduction of RotaTeq into the Israeli national immunization program...
October 19, 2016: Vaccine
Arend Voorman, Hil M Lyons
The Global Polio Eradication Initiative is closer than ever to achieving a polio-free world. Immunization activities must still be carried out in non-endemic countries to maintain population immunity at levels which will stop poliovirus from spreading if it is re-introduced from still-infected areas. In areas where there is no active transmission of poliovirus, programs must rely on surrogate indicators of population immunity to determine the appropriate immunization activities, typically caregiver-reported vaccination history obtained from non-polio acute flaccid paralysis patients identified through polio surveillance...
October 19, 2016: Vaccine
M Topuridze, D Baliashvili, T Komakhidze, M Shishniashvili, N Grdzelidze, M Butsashvili
Rotavirus (RV) is the most common cause of severe gastroenteritis in infants and young children worldwide. RV causes approximately half a million deaths each year among children aged <5 years. According to WHO estimates for 2008, there were approximately 10 to 50 deaths annually in young children due to rotavirus diarrhea in Georgia. The purpose of this study was to assess the knowledge, attitudes, and practices related to rotavirus diarrhea and the rotavirus vaccine among health care workers (HCWs). The National Center for Disease Control and Public Health (NCDC) conducted a cross-sectional survey of HCWs involved in the expanded program of immunization (EPI)...
September 2016: Georgian Medical News
Junsik Park, Minsuk Kwon, Eui-Cheol Shin
During immune responses antigen-specific T cells are regulated by several mechanisms, including through inhibitory receptors and regulatory T cells, to avoid excessive or persistent immune responses. These regulatory mechanisms, which are called 'immune checkpoints', suppress T cell responses, particularly in patients with chronic viral infections and cancer where viral antigens or tumor antigens persist for a long time and contribute to T cell exhaustion. Among these regulatory mechanisms, cytotoxic T lymphocyte associated protein-4 (CTLA-4) and programmed cell death 1 (PD-1) are the most well-known receptors and both have been targeted for drug development...
October 21, 2016: Archives of Pharmacal Research
C Franklin, E Livingstone, A Roesch, B Schilling, D Schadendorf
Malignant melanoma contributes the majority of skin cancer related deaths and shows an increasing incidence in the past years. Despite all efforts of early diagnosis, metastatic melanoma still has a poor prognosis and remains a challenge for treating physicians. In recent years, improved knowledge of the pathophysiology and a better understanding of the role of the immune system in tumour control have led to the development and approval of several immunotherapies. Monoclonal antibodies against different immune checkpoints have been revolutionizing the treatment of metastatic and unresectable melanoma...
September 2, 2016: European Journal of Surgical Oncology
Nitin Chakravarti, Doina Ivan, Van A Trinh, Isabella C Glitza, Jonathan L Curry, Carlos Torres-Cabala, Michael T Tetzlaff, Roland L Bassett, Victor G Prieto, Wen-Jen Hwu
Ipilimumab, a fully human monoclonal antibody against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), is the first immune checkpoint inhibitor approved for the treatment of unresectable melanoma on the basis of its overall survival (OS) benefit. However, ipilimumab is associated with significant immune-related adverse events. We hypothesized that biomarker exploration of pretreatment tumor samples and correlation with clinical outcome would enable patient selection with an increased benefit/risk ratio for ipilimumab therapy...
October 20, 2016: Melanoma Research
Ashton A Connor, Robert E Denroche, Gun Ho Jang, Lee Timms, Sangeetha N Kalimuthu, Iris Selander, Treasa McPherson, Gavin W Wilson, Michelle A Chan-Seng-Yue, Ivan Borozan, Vincent Ferretti, Robert C Grant, Ilinca M Lungu, Eithne Costello, William Greenhalf, Daniel Palmer, Paula Ghaneh, John P Neoptolemos, Markus Buchler, Gloria Petersen, Sarah Thayer, Michael A Hollingsworth, Alana Sherker, Daniel Durocher, Neesha Dhani, David Hedley, Stefano Serra, Aaron Pollett, Michael H A Roehrl, Prashant Bavi, John M S Bartlett, Sean Cleary, Julie M Wilson, Ludmil B Alexandrov, Malcolm Moore, Bradly G Wouters, John D McPherson, Faiyaz Notta, Lincoln D Stein, Steven Gallinger
Importance: Outcomes for patients with pancreatic ductal adenocarcinoma (PDAC) remain poor. Advances in next-generation sequencing provide a route to therapeutic approaches, and integrating DNA and RNA analysis with clinicopathologic data may be a crucial step toward personalized treatment strategies for this disease. Objective: To classify PDAC according to distinct mutational processes, and explore their clinical significance. Design, Setting, and Participants: We performed a retrospective cohort study of resected PDAC, using cases collected between 2008 and 2015 as part of the International Cancer Genome Consortium...
October 20, 2016: JAMA Oncology
J E Isenor, N T Edwards, T A Alia, K L Slayter, D M MacDougall, S A McNeil, S K Bowles
BACKGROUND: Underutilization of vaccination programs remains a significant public health concern. Pharmacists serve as educators, facilitators, and in some jurisdictions, as administrators of vaccines. Though pharmacists have been involved with immunizations in various ways for many years, there has yet to be a systematic review assessing the impact of pharmacists as immunizers in these three roles. OBJECTIVE: To complete a systematic review of the literature on the impact of pharmacists as educators, facilitators, and administrators of vaccines on immunization rates...
October 17, 2016: Vaccine
Yoshio Nakamura, Shigehisa Kitano, Akira Takahashi, Arata Tsutsumida, Kenjiro Namikawa, Keiji Tanese, Takayuki Abe, Takeru Funakoshi, Noboru Yamamoto, Masayuki Amagai, Naoya Yamazaki
BACKGROUND: An anti-programmed cell death protein 1 monoclonal antibody, nivolumab, is one of the most effective drugs for advanced melanoma. Tumor cell-derived or immune cell-derived markers and clinical predictors such as serum lactate dehydrogenase (LDH) and cutaneous adverse events, have already been described as prognostic factors for advanced melanoma treated with nivolumab. We sought to identify further clinical predictors that can be determined in routine clinical practice. METHODS: We retrospectively analyzed clinical findings of 98 consecutive patients with unresectable stage III or IV melanoma treated with nivolumab, at the National Cancer Center Hospital or at Keio University Hospital, in Tokyo, Japan, between July 2014 and July 2016...
October 15, 2016: Oncotarget
Antonin Levy, Christophe Massard, Jean-Charles Soria, Eric Deutsch
PURPOSE: To assess preliminary safety and efficacy results of the anti-programmed cell death ligand-1 (anti-PD-L1) durvalumab in combination with radiotherapy (RT) in an expansion cohort of patients included in a phase 1/2 trial at our institution. PATIENTS AND METHODS: Data from patients who received concurrent palliative RT with durvalumab (10 mg/kg every 2 weeks via intravenous infusion) were analysed in terms of safety (CTCAE v4.0) and efficacy (RECIST v1.1 and tumour growth rate [TGR])...
October 17, 2016: European Journal of Cancer
Anagha Loharikar, Laure Dumolard, Susan Chu, Terri Hyde, Tracey Goodman, Carsten Mantel
Since the global Expanded Program on Immunization (EPI) was launched in 1974, vaccination against six diseases (tuberculosis, polio, diphtheria, tetanus, pertussis, and measles) has prevented millions of deaths and disabilities (1). Significant advances have been made in the development and introduction of vaccines, and licensed vaccines are now available to prevent 25 diseases (2,3). Historically, new vaccines only became available in low-income and middle-income countries decades after being introduced in high-income countries...
October 21, 2016: MMWR. Morbidity and Mortality Weekly Report
Earnestine Willis, Svapna Sabnis, Chelsea Hamilton, Fue Xiong, Keli Coleman, Matt Dellinger, Michelle Watts, Richard Cox, Janice Harrell, Dorothy Smith, Melodee Nugent, Pippa Simpson
No abstract text is available yet for this article.
2016: Progress in Community Health Partnerships: Research, Education, and Action
Kipp Weiskopf, Peter J Schnorr, Wendy W Pang, Mark P Chao, Akanksha Chhabra, Jun Seita, Mingye Feng, Irving L Weissman
The hematopoietic stem cell (HSC) is a multipotent stem cell that resides in the bone marrow and has the ability to form all of the cells of the blood and immune system. Since its first purification in 1988, additional studies have refined the phenotype and functionality of HSCs and characterized all of their downstream progeny. The hematopoietic lineage is divided into two main branches: the myeloid and lymphoid arms. The myeloid arm is characterized by the common myeloid progenitor and all of its resulting cell types...
October 2016: Microbiology Spectrum
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