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https://www.readbyqxmd.com/read/30121453/targeting-myeloid-derived-suppressor-cells-using-all-trans-retinoic-acid-in-melanoma-patients-treated-with-ipilimumab
#1
Richard P Tobin, Kimberly R Jordan, William A Robinson, Dana Davis, Virginia F Borges, Rene Gonzalez, Karl D Lewis, Martin D McCarter
BACKGROUND: Immune checkpoint inhibitors have improved overall survival rates for many cancers, yet the majority of patients do not respond to treatment and succumb to disease progression. One tumor-related mechanism limiting the efficacy of immunotherapies in melanoma is the recruitment and expansion of myeloid-derived suppressor cells (MDSCs). Therefore, targeting MDSCs in combination with immunotherapies is an attractive strategy to improve response rates and effectiveness. METHODS: We tested this strategy by designing a randomized phase II clinical trial treating advanced melanoma patients with either Ipilimumab monotherapy or Ipilimumab plus all-trans retinoic acid (ATRA)...
August 16, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/30121330/nanoengineered-delivery-systems-for-cancer-imaging-and-therapy-recent-advances-future-directions-and-patent-evaluation
#2
REVIEW
Ghazal Nabil, Ketki Bhise, Samaresh Sau, Mohamed Atef, Hossny A El-Banna, Arun K Iyer
Cancer is the second-highest cause of death worldwide. Several therapeutic approaches, such as conventional chemotherapy, antibodies and small-molecule inhibitors and nanotherapeutics, have been employed in battling cancer. Among them, nanotheranostics is an example of successful personalized medicine bearing the dual role of early diagnosis and therapy to cancer patients. In this review, we focus on various types of theranostic polymer and metal nanoparticles for their roles in cancer therapy and imaging concerning their limitations and future applications, such as dendritic cell cancer vaccination, gene delivery, T cell activation and immune modulation...
August 16, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30121234/the-prognostic-significance-of-p16-status-in-patients-with-vulvar-cancer-treated-with-vulvectomy-and-adjuvant-radiation
#3
Michael J Dohopolski, Zachary D Horne, Dinesh Pradhan, Rohit Bhargava, Robert P Edwards, Joseph L Kelley, John T Comerci, Alexander B Olawaiye, Madeleine Courtney-Brooks, Jessica L Berger, Paniti Sukumvanich, Sushil Beriwal
PURPOSE: Vulvar squamous cell carcinoma (VSCC) is a relatively rare malignancy. Human papillomavirus (HPV) has been implicated as a causative factor for a subset of these patients. The purpose of this study is to evaluate if p16-positivity (an HPV surrogate) predicts for better response rates in women who undergo surgery followed by adjuvant radiation therapy (RT). METHODS: We retrospectively analyzed women with VSCC who were treated with adjuvant RT. p16-positivity was defined as diffuse strong immunoreactivity within the tumor...
August 16, 2018: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/30120895/human-cancer-evolution-in-the-context-of-a-human-immune-system-in-mice
#4
Odd L Gammelgaard, Mikkel G Terp, Birgitte Preiss, Henrik J Ditzel
Immunotherapy is one of the most promising cancer treatment modalities, but the lack of appropriate preclinical in vivo models hampers the development of novel immunotherapeutic strategies. Here, we studied the ability of transplanted human cancer cells to form primary tumors and metastasize in humanized immune system mice created by transfer of CD34+ human hematopoietic stem cells. All tested transplanted cancer cell lines developed primary tumors that progressed nearly synchronously. Spontaneous lung and liver metastases developed from both orthotopic and ectotopic transplanted cancer cells, and the ability to spread inversely correlated with the extent of CD8+ infiltration in the primary tumor...
August 18, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/30120103/baseline-cytokine-profiles-of-tuberculin-specific-cd4-t-cells-in-non-muscle-invasive-bladder-cancer-may-predict-outcomes-of-bcg-immunotherapy
#5
Samer Jallad, Philip Thomas, Melanie J Newport, Florian Kern
Intravesical Bacillus Calmette-Guérin (BCG) immunotherapy preserves the bladder after resection of high-risk non-muscle invasive bladder cancer (NMIBC). About 30% of patients experience treatment failure, which cannot be predicted a priori and carries a high risk of disease progression. We examined the in vitro tuberculin-responsiveness of CD4+ T cells before BCG immunotherapy in 42 patients with high-risk NMIBC. The frequencies and functionalities of cytokine-expressing CD4+ T cells immediately before and after BCG immunotherapy induction were assessed by flow cytometry after overnight tuberculin stimulation...
August 17, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/30120013/management-of-immune-checkpoint-inhibitor-toxicities-a-review-and-clinical-guideline-for-emergency-physicians
#6
Adam T Hryniewicki, Claire Wang, Rebecca A Shatsky, Christopher J Coyne
BACKGROUND: Immune checkpoint inhibitors (ICIs) are a novel class of drugs used in cancer immunotherapy that are becoming more commonly used among advanced-stage cancers. Unfortunately, these therapies are sometimes associated with often subtle, potentially fatal immune-related adverse events (irAEs). OBJECTIVES: We conducted a review of relevant primary research and clinical guidelines in oncology, pharmacology, and other literature, and synthesized this information to address the needs of the emergency physician in the acute management of irAEs...
August 14, 2018: Journal of Emergency Medicine
https://www.readbyqxmd.com/read/30119830/-the-car-t-cells-are-here
#7
Carolyne Croizier, Aurore Douge, Jacques-Olivier Bay, Richard Lemal
Due to immunotherapy, a new era of treatment is opening up for the treatment of solid cancers and hematological tumors. T cells genetically modified with a chimeric antigen receptor (CAR-T cells) have recently been proved efficient in hematological malignancies expressing CD19. On June 20th 2018, the European Medicines Agency gave a favorable opinion on two types of anti-CD19 CAR-T cells - tisagenlecleucel and axicabtagène ciloleucel - in the management of malignant hemopathies B after two lines of treatment...
August 14, 2018: Bulletin du Cancer
https://www.readbyqxmd.com/read/30119083/combinations-of-bevacizumab-with-cancer-immunotherapy
#8
Daniel S Chen, Herbert Hurwitz
Cancer immunotherapy (CIT) has transformed cancer treatment. In particular, immunotherapies targeting the programmed death ligand 1 (PD-L1)/programmed death 1 pathway have demonstrated durable clinical benefit in some patients. However, CIT combinations may create a more favorable environment in which to maximize the potential of the immune system to eliminate cancer. Here we describe 3 key mechanisms related to vascular endothelial growth factor (VEGF)-mediated immunosuppression: inhibition of dendritic cell maturation, reduction of T-cell tumor infiltration, and promotion of inhibitory cells in the tumor microenvironment; supporting data are also described...
July 2018: Cancer Journal
https://www.readbyqxmd.com/read/30118965/clinical-and-genetic-signatures-of-local-recurrence-in-oral-squamous-cell-carcinoma
#9
Yasmine Ghantous, Zaher Bahouth, Imad Abu El-Naaj
PURPOSE: Recurrent and metastatic Oral Squamous Cell Carcinoma (OSCC) is often incurable. There are large gaps in the understanding of the clinical course, biology and genetic biomarkers of OSCC which could help us identify patients with high-risk of recurrence who may benefit from intensified therapy or novel targeted therapy trials. The purpose of this study was to identify significant clinical, pathological and genomic risk factors for local recurrence in OSCC. PATIENTS AND METHODS: Molecular data sets and clinicopathological characteristics of 159 head and neck carcinoma patients were obtained from The Cancer Genome Atlas (TCGA) data portal and analyzed using the Genome Data Analysis Center and cBioPortal to find significant risk factors for tumor recurrence...
August 6, 2018: Archives of Oral Biology
https://www.readbyqxmd.com/read/30118659/functional-characterization-of-alternatively-spliced-gsn-in-head-and-neck-squamous-cell-carcinoma
#10
D Z Kelley, E L Flam, T Guo, L V Danilova, F Zamuner, C Bohrson, M Considine, E J Windsor, J A Bishop, C Zhang, W M Koch, D Sidransky, W H Westra, C H Chung, J A Califano, S Wheelan, A V Favorov, L Florea, E J Fertig, D A Gaykalova
We have recently performed the characterization of alternative splicing events (ASEs) in head and neck squamous cell carcinoma, which allows dysregulation of protein expression common for cancer cells. Such analysis demonstrated a high ASE prevalence among tumor samples, including tumor-specific alternative splicing in the GSN gene. In vitro studies confirmed that overall expression of either ASE-GSN or wild-type GSN (WT-GSN) isoform inversely correlated with cell proliferation, whereas the high ratio of ASE-GSN to WT-GSN correlated with increased cellular invasion...
July 26, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30117062/anti-pd-1-treatment-increases-18-f-fdg-uptake-by-cancer-cells-in-a-mouse-b16f10-melanoma-model
#11
Mayu Tomita, Hironobu Yasui, Kei Higashikawa, Kohei Nakajima, Hideo Takakura, Tohru Shiga, Yuji Kuge, Mikako Ogawa
BACKGROUND: Programmed cell death 1 (PD-1) inhibitors act as immune checkpoint inhibitors and are more effective for improving survival time with less toxicity as compared with conventional chemotherapies. In anti PD-1 therapy, it is important to evaluate metabolism in the cancer microenvironment, as this helps to clarify the pathological conditions. Herein, we investigate the early effects of PD-1 therapy on 2-deoxy-2-[18 F]fluoro-D-glucose ([18 F]FDG) uptake in vivo, focusing on cell distribution and glycolysis in both cancer and immune cells...
August 16, 2018: EJNMMI Research
https://www.readbyqxmd.com/read/30116994/drug-induced-expression-of-epcam-contributes-to-therapy-resistance-in-esophageal-adenocarcinoma
#12
Xuan Sun, Robert C G Martin, Qianqian Zheng, Russell Farmer, Harshul Pandit, Xuanyi Li, Kevin Jacob, Jian Suo, Yan Li
BACKGROUND: With a less than 5% overall survival rate, esophageal adenocarcinoma (EAC) is one of the leading causes of death in the United States. Epithelial cell adhesion molecule (EpCAM) is a cancer stem cell (CSC) marker that is expressed in various epithelial carcinomas, including EAC. Accumulating evidence indicates that CSC subpopulations can initiate cancer development and, in addition, drive metastasis, recurrence and drug resistance. It has also been reported that EpCAM up-regulation in EAC may lead to an aggressive behavior and, thus, an adverse clinical outcome...
August 16, 2018: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/30116358/natural-killer-cells-inhibit-metastasis-of-ovarian-carcinoma-cells-and-show-therapeutic-effects-in-a-murine-model-of-ovarian-cancer
#13
Yanming Sun, Zhitao Yao, Zhihua Zhao, Haifeng Xiao, Mengting Xia, Xiaojun Zhu, Xuelu Jiang, Chuntao Sun
Ovarian cancer has the highest mortality rate and is the most common of all gynecologic malignancies. Novel treatments for ovarian cancer are urgently required to improve outcomes and the overall survival of patients. The present study investigated whether immunotherapy with natural killer (NK) cells affected the survival of mice with ovarian cancer. Results analysis identified adjunctive NK cells as a potential therapeutic method in ovarian cancer. Patient-derived ovarian cells were isolated, cultured and subsequently injected subcutaneously into immune deficient BALB/c-nude mice...
August 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/30115740/identification-of-non-mutated-neoantigens-presented-by-tap-deficient-tumors
#14
Koen A Marijt, Laura Blijleven, Els M E Verdegaal, Michel G Kester, Daniel J Kowalewski, Hans-Georg Rammensee, Stefan Stevanović, Mirjam H M Heemskerk, Sjoerd H van der Burg, Thorbald van Hall
Most T cell-based immunotherapies of cancer depend on intact antigen presentation by HLA class I molecules (HLA-I). However, defects in the antigen-processing machinery can cause downregulation of HLA-I, rendering tumor cells resistant to CD8+ T cells. Previously, we demonstrated that a unique category of cancer antigens is selectively presented by tumor cells deficient for the peptide transporter TAP, enabling a specific attack of such tumors without causing immunopathology in mouse models. With a novel combinatorial screening approach, we now identify 16 antigens of this category in humans...
August 16, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/30115704/fundamental-mechanisms-of-immune-checkpoint-blockade-therapy
#15
REVIEW
Spencer C Wei, Colm R Duffy, James P Allison
Immune checkpoint blockade is able to induce durable responses across multiple types of cancer, which has enabled the oncology community to begin to envision potentially curative therapeutic approaches. However, the remarkable responses to immunotherapies are currently limited to a minority of patients and indications, highlighting the need for more effective and novel approaches. Indeed, an extraordinary amount of preclinical and clinical investigation is exploring the therapeutic potential of negative and positive costimulatory molecules...
August 16, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30115471/clinical-analysis-of-second-primary-gingival-squamous-cell-carcinoma-after-radiotherapy
#16
Xiaoyan Fu, Shuwei Chen, Weichao Chen, Zhongyuan Yang, Ming Song, Hao Li, Huayong Zhang, Fan Yao, Xuan Su, Tianrun Liu, An-Kui Yang
INTRODUCTION: Clinically, we have observed that some oral cancer patients have a history of radiotherapy for head and neck cancer; we have named this condition radiotherapy-associated cancer (RAC). Gingival cancer, which is usually juxtaposed with other oral cancer subtypes, is seldom reported individually, and there are few reports on the association between the incidence of oral cancer and history of radiation therapy. Therefore, this study aimed to elucidate the clinicopathological features and prognosis of second primary gingival squamous cell carcinoma after head and neck radiotherapy...
September 2018: Oral Oncology
https://www.readbyqxmd.com/read/30114461/knowledge-based-planning-for-identifying-high-risk-stereotactic-ablative-radiotherapy-treatment-plans-for-lung-tumors-larger-than-5cm
#17
Saar van T Hof, Alexander R Delaney, Hilâl Tekatli, Jos Twisk, Ben J Slotman, Suresh Senan, Max Dahele, Wilko Far Verbakel
PURPOSE: Stereotactic ablative body radiotherapy (SABR) for lung tumors ≥5cm, can be associated with more toxicity. We investigated the relationship between dosimetry and toxicity and used a knowledge-based planning solution to retrospectively perform individualized treatment plan quality assurance (QA) with the aim of identifying where planning could have been improved. MATERIAL AND METHODS: Prior retrospective analysis of 53 patients with primary or recurrent non-small cell lung cancer ≥5cm, treated with 5 or 8-fraction volumetric modulated arc therapy SABR, between 2008-2014, showed 30% ≥grade (G) 3 toxicity...
August 13, 2018: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/30113582/-the-analysis-of-the-association-of-the-polymorphic-variants-of-the-tpmt-comt-and-abcc3-genes-with-the-development-of-hearing-disorders-induced-by-the-cisplatin-treatment
#18
O L Mironovich, E A Bliznetz, E S Garbaruk, M B Belogurova, N V Subora, S R Varfolomeeva, D Yu Kachanov, T V Shamanskaya, T G Markova, A V Polyakov
Cisplatin and its derivatives are widely used chemotherapeutic agents for the treatment of many cancers, including hepatoblastoma, brain tumors, and germ-cell tumors. This therapy contributed to the dramatic increase in the survival rate. However, its use is restricted by the high incidence of irreversible ototoxicity associated with cisplatin application (in more than 60% of the children receiving it). Some studies have reported that genetic variants of TPMT (rs 12201199), COMT (rs4646316), and ABCC3 (rs 1051640) are conferring increased risk of developing cisplatin-induced hearing loss...
2018: Vestnik Otorinolaringologii
https://www.readbyqxmd.com/read/30112704/in-vivo-imaging-of-the-immune-response-upon-systemic-rna-cancer-vaccination-by-fdg-pet
#19
Stefanie Pektor, Lina Hilscher, Kerstin C Walzer, Isabelle Miederer, Nicole Bausbacher, Carmen Loquai, Mathias Schreckenberger, Ugur Sahin, Mustafa Diken, Matthias Miederer
BACKGROUND: [18 F]Fluoro-2-deoxy-2-D-glucose positron emission tomography (FDG-PET) is commonly used in the clinic for diagnosis of cancer and for follow-up of therapy outcome. Additional to the well-established value in tumor imaging, it bears potential to depict immune processes in modern immunotherapies. T cells enhance their glucose consumption upon activation and are crucial effectors for the success of such novel therapies. In this study, we analyzed the T cell immunity in spleen after antigen-specific stimulation of T cells via highly innovative RNA-based vaccines using FDG-PET/MRI...
August 15, 2018: EJNMMI Research
https://www.readbyqxmd.com/read/30112696/a-method-for-expansion-of-t-cells-from-cynomolgus-monkey-macaca-fascicularis
#20
Change Gao, Qian Song, Ming Zhang, Jian Li, Miao Yi, Jian Dong
T cells have been successfully applied to cancer immunotherapy. However, a challenge is an expansion of T cells from cynomolgus monkey, which is a valuable non-human primate model for T cell therapy transferring to the clinic. Here, we compared several strategies to expand cynomolgus monkey T cell and developed an appropriate method. Our study demonstrated that 100 ng/ml CD3 mAb + 1% PHA+ 1000 U/ml IL2 therapy significantly expanded peripheral blood CD3+ T cells without compromising T cell phenotype in vitro...
August 15, 2018: In Vitro Cellular & Developmental Biology. Animal
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