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Cancer immunotherapy

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https://www.readbyqxmd.com/read/28550027/exceptional-response-to-nivolumab-and-stereotactic-body-radiation-therapy-sbrt-in-neuroendocrine-cervical-carcinoma-with-high-tumor-mutational-burden-management-considerations-from-the-center-for-personalized-cancer-therapy-at-uc-san-diego-moores-cancer-center
#1
Andrew Sharabi, Sangwoo Shawn Kim, Shumei Kato, Philip D Sanders, Sandip Pravin Patel, Parag Sanghvi, Elizabeth Weihe, Razelle Kurzrock
Neuroendocrine carcinoma of the cervix is an ultra-rare malignancy with a poor prognosis and limited treatment options. Checkpoint blockade immunotherapy has rapidly developed into an emerging standard of care for several common disease types. Interestingly, in preclinical and retrospective clinical data, radiation therapy has been demonstrated to synergize with checkpoint inhibitors. Here we report a patient with metastatic, chemotherapy-refractory neuroendocrine carcinoma who presented with partial bowel obstruction due to a large tumor burden...
May 26, 2017: Oncologist
https://www.readbyqxmd.com/read/28549917/dendritic-cell-derived-exosomes-elicit-tumor-regression-in-autochthonous-hepatocellular-carcinoma-mouse-models
#2
Zhen Lu, Bingfeng Zuo, Renwei Jing, Xianjun Gao, Quan Rao, Zhili Liu, Han Qi, Hongxing Guo, HaiFang Yin
BACKGROUND & AIMS: Dendritic cell (DC)-derived exosomes (DEXs) form a new class of vaccines for cancer immunotherapy. However their potency in hepatocellular carcinoma (HCC), a life-threatening malignancy with limited treatment options in the clinic and responds poorly to immunotherapy, remains to be investigated. METHODS: Exosomes derived from α-fetoprotein (AFP) - expressing DCs (DEXAFP) were investigated in three different HCC mouse models systemically and tumor growth and microenvironment were monitored...
May 23, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28549039/paired-comparison-of-pd-l1-expression-on-cytologic-and-histologic-specimens-from-malignancies-in-the-lung-assessed-with-pd-l1-ihc-28-8pharmdx-and-pd-l1-ihc-22c3pharmdx
#3
Birgit G Skov, Torsten Skov
BACKGROUND: Programmed cell death ligand-1 (PD-L1) expression is a predictive biomarker for anti-PD-1 immunotherapy in non-small cell lung cancer. Different immunohistochemistry (IHC) assays have been developed on histologic material with different cutoffs for positivity. More than one third of the patients are diagnosed on cytology alone. We hypothesized that cytologic cell block material is suitable for PD-L1 analysis. MATERIALS AND METHODS: Eighty-six paired samples of malignancies from the lung where cytologic cell block and histologic material were available from the same lesion were stained with PD-L1 IHC 28-8pharmDx and PD-L1 IHC 22C3pharmDx...
May 25, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28548132/tumour-immunology-platelets-a-new-target-in-cancer-immunotherapy
#4
Yvonne Bordon
No abstract text is available yet for this article.
May 26, 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28548102/replicating-viral-vector-platform-exploits-alarmin-signals-for-potent-cd8-t-cell-mediated-tumour-immunotherapy
#5
Sandra M Kallert, Stephanie Darbre, Weldy V Bonilla, Mario Kreutzfeldt, Nicolas Page, Philipp Müller, Matthias Kreuzaler, Min Lu, Stéphanie Favre, Florian Kreppel, Max Löhning, Sanjiv A Luther, Alfred Zippelius, Doron Merkler, Daniel D Pinschewer
Viral infections lead to alarmin release and elicit potent cytotoxic effector T lymphocyte (CTL(eff)) responses. Conversely, the induction of protective tumour-specific CTL(eff) and their recruitment into the tumour remain challenging tasks. Here we show that lymphocytic choriomeningitis virus (LCMV) can be engineered to serve as a replication competent, stably-attenuated immunotherapy vector (artLCMV). artLCMV delivers tumour-associated antigens to dendritic cells for efficient CTL priming. Unlike replication-deficient vectors, artLCMV targets also lymphoid tissue stroma cells expressing the alarmin interleukin-33...
May 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28547807/tnfsf9-exerts-an-inhibitory-effect-on-hepatocellular-carcinoma
#6
Yuling Shen, Yu Gan, Haifeng Gao, Yingchao Fan, Qing Wang, Hui Yuan, Yanfang Song, Jiadong Wang, Hong Tu
AIM: Tumor necrosis factor superfamily member 9 (TNFSF9), also known as 4-1BBL and CD137L, has been implicated in cancer immunotherapy due to its function as a T cell costimulator. However, little is known about its direct impact on cancer development, particularly for solid tumors. METHODS: The TNFSF9 expression was examined by immunohistochemistry in 106 pairs of hepatocellular carcinoma (HCC) and the adjacent non-HCC tissues, and by quantitative PCR and Western blot in HCC cell lines...
May 26, 2017: Journal of Digestive Diseases
https://www.readbyqxmd.com/read/28546954/pleiotropic-cytotoxicity-of-vaca-toxin-in-host-cells-and-its-impact-on-immunotherapy
#7
REVIEW
Farnaz Fahimi, Mohammad Reza Tohidkia, Mehdi Fouladi, Reza Aghabeygi, Naser Samadi, Yadollah Omidi
Introduction: In the recent decades, a number of studies have highlighted the importance of Helicobacter pylori in the initiation and development of peptic ulcer and gastric cancer. Some potential virulence factors (e.g., urease, CagA, VacA, BabA) are exploited by this microorganism, facilitating its persistence through evading human defense mechanisms. Among these toxins and enzymes, vacuolating toxin A (VacA) is of a great importance in the pathogenesis of H. pylori. VacA toxin shows different pattern of cytotoxicity through binding to different cell surface receptors in various cells...
2017: BioImpacts: BI
https://www.readbyqxmd.com/read/28546756/new-developments-in-the-treatment-of-advanced-squamous-cell-lung-cancer-focus-on-afatinib
#8
REVIEW
Vera Hirsh
Until recently, few treatment options existed for the treatment of squamous cell carcinoma (SqCC) of the lung, especially in the second-line setting following platinum-based chemotherapy. Accordingly, outcomes in this subtype of non-small-cell lung cancer (NSCLC) were generally poor. In this context, the recent availability of the checkpoint inhibitors nivolumab and pembrolizumab, the anti-VEGFR2 antibody ramucirumab (combined with docetaxel), and the ErbB-family blocker afatinib for the treatment of relapsed/refractory SqCC of the lung represent major advances...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28546500/myeloid-derived-suppressor-cells-a-new-therapeutic-target-to-overcome-resistance-to-cancer-immunotherapy
#9
REVIEW
Jason A Chesney, Robert A Mitchell, Kavitha Yaddanapudi
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that accumulate during pathologic conditions, such as cancer. Patients diagnosed with advanced metastatic cancers have an average survival of 12-24 mo, a survival time that hasn't changed significantly in the past 30 yr. Despite some encouraging improvements in response rates and overall survival in patients receiving immunotherapies, such as immune checkpoint inhibitors, most patients will ultimately progress...
May 25, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28546287/immune-atlases-created-for-kidney-lung-cancers
#10
(no author information available yet)
Two groups of researchers have generated the first comprehensive "immune atlases" of clear cell renal cell carcinoma and early lung adenocarcinoma. Their work better illuminates the tumor immune microenvironment and may lead to more effective immunotherapy strategies.
May 25, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28545888/delivering-safer-immunotherapies-for-cancer
#11
Lauren Milling, Yuan Zhang, Darrell J Irvine
Cancer immunotherapy is now a powerful clinical reality, with a steady progression of new drug approvals and a massive pipeline of additional treatments in clinical and preclinical development. However, modulation of the immune system can be a double-edged sword: Drugs that activate immune effectors are prone to serious non-specific systemic inflammation and autoimmune side effects. Drug delivery technologies have an important role to play in harnessing the power of immune therapeutics while avoiding on-target/off-tumor toxicities...
May 22, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28545567/cancer-immunotherapy-by-targeting-immune-checkpoints-mechanism-of-t-cell-dysfunction-in-cancer-immunity-and-new-therapeutic-targets
#12
REVIEW
Hwei-Fang Tsai, Ping-Ning Hsu
Immune checkpoints or coinhibitory receptors, such as cytotoxic T lymphocyte antigen (CTLA)-4 and programmed death (PD)-1, play important roles in regulating T cell responses, and they were proven to be effective targets in treating cancer. In chronic viral infections and cancer, T cells are chronically exposed to persistent antigen stimulation. This is often associated with deterioration of T cell function with constitutive activation of immune checkpoints, a state called 'exhaustion', which is commonly associated with inefficient control of tumors and persistent viral infections...
May 25, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28545552/hrhpv-e5-oncoprotein-immune-evasion-and-related-immunotherapies
#13
REVIEW
Antonio Carlos de Freitas, Talita Helena Araújo de Oliveira, Marconi Rego Barros, Aldo Venuti
The immune response is a key factor in the fight against HPV infection and related cancers, and thus, HPV is able to promote immune evasion through the expression of oncogenes. In particular, the E5 oncogene is responsible for modulation of several immune mechanisms, including antigen presentation and inflammatory pathways. Moreover, E5 was suggested as a promising therapeutic target, since there is still no effective medical therapy for the treatment of HPV-related pre-neoplasia and cancer. Indeed, several studies have shown good prospective for E5 immunotherapy, suggesting that it could be applied for the treatment of pre-cancerous lesions...
May 25, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28545238/epigenetic-strategies-to-boost-cancer-immunotherapies
#14
REVIEW
Maria J Barrero
Recently, immunotherapeutic approaches have shown impressive responses in a subset of cancer patients. However, the rate of success is low and a large percentage of treated patients do not experience clinical benefits. Therefore, additional strategies are needed to improve responses and select responsive patients. Emerging data suggest that epigenetic drugs can improve the responses to immunotherapy. Understanding the mechanisms of resistance to immunotherapy and the epigenetic events that take place during immune evasion is critical to providing a rational combined use of immunotherapies and epigenetic drugs...
May 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28544821/predictive-model-for-high-frequency-microsatellite-instability-in-colorectal-cancer-patients-over-50%C3%A2-years-of-age
#15
Kenji Fujiyoshi, Tatsuro Yamaguchi, Miho Kakuta, Akemi Takahashi, Yoshiko Arai, Mina Yamada, Gou Yamamoto, Sachiko Ohde, Misato Takao, Shin-Ichiro Horiguchi, Soichiro Natsume, Shinsuke Kazama, Yusuke Nishizawa, Yoji Nishimura, Yoshito Akagi, Hirohiko Sakamoto, Kiwamu Akagi
Microsatellite instability (MSI) is an important biomarker for screening for Lynch syndrome, and also of response to immune checkpoint inhibitors. The aim of this study is to create a predictive model to determine which elderly patients with colorectal cancer (CRC) should undergo MSI and/or immunohistochemistry testing on the basis of clinicopathological data. We analyzed a test cohort of CRC patients aged ≥50 years (n = 2219) by multivariate logistic regression analyses to identify predictors of high-frequency MSI (MSI-H)...
May 23, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28544818/ubiquitination-in-melanoma-pathogenesis-and-treatment
#16
REVIEW
Jinyuan Ma, Weinan Guo, Chunying Li
Melanoma is one of the most aggressive skin cancers with fiercely increasing incidence and mortality. Since the progressive understanding of the mutational landscape and immunologic pathogenic factors in melanoma, the targeted therapy and immunotherapy have been recently established and gained unprecedented improvements for melanoma treatment. However, the prognosis of melanoma patients remains unoptimistic mainly due to the resistance and nonresponse to current available drugs. Ubiquitination is a posttranslational modification which plays crucial roles in diverse cellular biological activities and participates in the pathogenesis of various cancers, including melanoma...
May 23, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28544801/nanotherapeutic-systems-for-local-treatment-of-brain-tumors
#17
REVIEW
Rami Walid Chakroun, Pengcheng Zhang, Ran Lin, Paula Schiapparelli, Alfredo Quinones-Hinojosa, Honggang Cui
Malignant brain tumor, including the most common type glioblastoma, are histologically heterogeneous and invasive tumors known as the most devastating neoplasms with high morbidity and mortality. Despite multimodal treatment including surgery, radiotherapy, chemotherapy, and immunotherapy, the disease inevitably recurs and is fatal. This lack of curative options has motivated researchers to explore new treatment strategies and to develop new drug delivery systems (DDSs); however, the unique anatomical, physiological, and pathological features of brain tumors greatly limit the effectiveness of conventional chemotherapy...
May 24, 2017: Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology
https://www.readbyqxmd.com/read/28544545/cytoprotective-encapsulation-of-individual-jurkat-t-cells-within-durable-tio2-shells-for-t-cell-therapy
#18
Wongu Youn, Eun Hyea Ko, Mi-Hee Kim, Matthew Park, Daewha Hong, Gulaim A Seisenbaeva, Vadim G Kessler, Insung S Choi
Lymphocytes, such as T cells and natural killer (NK) cells, have therapeutic promises in adoptive cell transfer (ACT) therapy, where the cells are activated and expanded in vitro, and then infused into a patient. However, the in vitro preservation of labile lymphocytes during transfer, manipulation, and storage has been one of the bottlenecks in the development and commercialization of therapeutic lymphocytes. Herein, we suggest a "cell-in-shell" (a.k.a. artificial spore) strategy to enhance the cell viability in the practical settings, while maintaining biological activities for therapeutic efficacy...
May 25, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28543700/interaction-of-molecular-alterations-with-immune-response-in-melanoma
#19
REVIEW
Robert A Szczepaniak Sloane, Vancheswaran Gopalakrishnan, Sangeetha M Reddy, Xue Zhang, Alexandre Reuben, Jennifer A Wargo
Major advances have been made in melanoma treatment with the use of molecularly targeted therapies and immunotherapies, and numerous regimens are now approved by the US Food and Drug Administration for patients with stage IV disease. However, therapeutic resistance remains an issue to both classes of agents, and reliable biomarkers of therapeutic response and resistance are lacking. Mechanistic insights are being gained through preclinical studies and translational research, offering potential strategies to enhance responses and survival in treated patients...
June 1, 2017: Cancer
https://www.readbyqxmd.com/read/28543699/immune-and-molecular-correlates-in-melanoma-treated-with-immune-checkpoint-blockade
#20
REVIEW
Elizabeth H Byrne, David E Fisher
Immunotherapy for metastatic melanoma has a decades-long history, and the relatively recent use of checkpoint inhibitors has revolutionized treatment. Durable and sometimes complete remission of metastatic melanoma is now achievable in some patients who receive checkpoint-blocking therapy. However, it is unclear why some patients fare better than others. This review highlights several molecular indicators of response to checkpoint inhibition in metastatic melanoma, focusing on tumor programmed death ligand 1 expression, major histocompatibility complex class I expression, mutational load in the tumor, and T-cell infiltration into the tumor...
June 1, 2017: Cancer
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