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immunotherapy of cancer

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https://www.readbyqxmd.com/read/28922848/aggressive-behavior-in-silent-subtype-iii-pituitary-adenomas-may-depend-on-suppression-of-local-immune-response-a-whole-transcriptome-analysis
#1
Timothy E Richardson, Zhong-Jian Shen, Mohammed Kanchwala, Chao Xing, Alexander Filatenkov, Ping Shang, Samuel Barnett, Zahidur Abedin, James S Malter, Jack M Raisanen, Dennis K Burns, Charles L White, Kimmo J Hatanpaa
Silent subtype III pituitary adenomas (SS-3) are clinically nonfunctional adenomas that are more aggressive in terms of invasion and risk of recurrence than their conventional null cell counterparts. We previously showed that these tumors can be distinguished by immunohistochemistry based on the identification of a markedly enlarged and fragmented Golgi apparatus. To understand the molecular correlates of differential aggressiveness, we performed whole transcriptome sequencing (RNAseq) on 4 SS-3 and 4 conventional null cell adenomas...
October 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28922411/cytokine-induced-killer-cell-delivery-enhances-the-antitumor-activity-of-oncolytic-reovirus
#2
Xing Zhao, Weiwei Ouyang, Cariad Chester, Shiqi Long, Nianxue Wang, Zhixu He
Oncolytic viruses (OV) have recently emerged as a promising therapeutic modality in cancer treatment. OV selectively infect and kill tumor cells, while sparing untransformed cells. The direct cytotoxic effects combined with the capacity to trigger an immune response make OV an appealing combination partner in the burgeoning field of cancer immunotherapy. One of the leading OV therapeutic candidates is the double-stranded RNA virus reovirus. In order to improve the oncolytic activity of reovirus and allow for systemic administration despite the prevalence of neutralizing antibodies, cytokine-induced killer (CIK) cells were explored as cell carriers for reovirus delivery...
2017: PloS One
https://www.readbyqxmd.com/read/28922238/primary-central-nervous-system-lymphoma-time-for-diagnostic-biomarkers-and-biotherapies
#3
Louis Royer-Perron, Khê Hoang-Xuan, Agusti Alentorn
PURPOSE OF REVIEW: Primary central nervous system lymphoma (PCNSL) is a rare cancer with a somber prognosis in older patients, which it affects predominantly. Only in recent years have molecular alterations characterizing PCNSL been thoroughly described. This opens possibilities for the use of targeted therapies. Developments in imaging and biomarkers have also great potential to help clinicians faced with diagnostic and prognostic uncertainties. RECENT FINDINGS: Several biomarkers for PCNSL, such as different microRNAs, which could be tested in cerebrospinal fluid and vitreous fluid, and IL-10, which has been shown to have excellent sensitivity and specificity in the cerebrospinal fluid, have emerged in the last years...
September 15, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28921946/biomimetic-magnetosomes-as-versatile-artificial-antigen-presenting-cells-to-potentiate-t-cell-based-anticancer-therapy
#4
Qianmei Zhang, Wei Wei, Peiling Wang, Liping Zuo, Feng Li, Jin Xu, Xiaobo Xi, Xiaoyong Gao, Guanghui Ma, Hai-Yan Xie
Adoptive T-cell transfer for cancer therapy relies on both effective ex vivo T cell expansion and in vivo targeting performance. One promising but challenging method for accomplishing this purpose is to construct multifunctional artificial antigen-presenting cells (aAPCs). We herein developed biomimetic magnetosomes as versatile aAPCs, wherein magnetic nanoclusters were coated with azide-engineered leucocyte membranes and then decorated with T-cell stimuli through copper-free click chemistry. These novel nano aAPCs not only exhibited high performance for antigen-specific cytotoxic T cell (CTL) expansion and stimulation but also visually and effectively guided reinfused CTLs to tumor tissues through magnetic resonance imaging and magnetic control...
September 18, 2017: ACS Nano
https://www.readbyqxmd.com/read/28921585/allergooncology-opposite-outcomes-of-immune-tolerance-in-allergy-and-cancer
#5
E Jensen-Jarolim, H J Bax, R Bianchini, S Crescioli, T R Daniels-Wells, D Dombrowicz, E Fiebiger, H J Gould, S Irshad, J Janda, D H Josephs, F Levi-Schaffer, L O Mahony, G Pellizzari, M L Penichet, F Redegeld, F Roth-Walter, J Singer, E Untersmayr, L Vangelista, S N Karagiannis
While desired for the cure of allergy, regulatory immune cell subsets and non-classical Th2-biased inflammatory mediators in the tumour microenvironment can contribute to immune suppression and escape of tumours from immunological detection and clearance. A key aim in the cancer field is therefore to design interventions that can break immunological tolerance and halt cancer progression, whereas on the contrary allergen immunotherapy exactly aims to induce tolerance. In this position paper, we review insights on immune tolerance derived from allergy and from cancer inflammation, focusing on what is known about the roles of key immune cells and mediators...
September 16, 2017: Allergy
https://www.readbyqxmd.com/read/28920587/complement-in-cancer-untangling-an-intricate-relationship
#6
REVIEW
Edimara S Reis, Dimitrios C Mastellos, Daniel Ricklin, Alberto Mantovani, John D Lambris
In tumour immunology, complement has traditionally been considered as an adjunctive component that enhances the cytolytic effects of antibody-based immunotherapies, such as rituximab. Remarkably, research in the past decade has uncovered novel molecular mechanisms linking imbalanced complement activation in the tumour microenvironment with inflammation and suppression of antitumour immune responses. These findings have prompted new interest in manipulating the complement system for cancer therapy. This Review summarizes our current understanding of complement-mediated effector functions in the tumour microenvironment, focusing on how complement activation can act as a negative or positive regulator of tumorigenesis...
September 18, 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28920006/dosing-immunotherapy-combinations-analysis-of-3-526-patients-for-toxicity-and-response-patterns
#7
Mina Nikanjam, Harsh Patel, Razelle Kurzrock
Immunotherapy combinations are used to improve outcomes in metastatic cancer, but evidence-based knowledge of appropriate starting doses for novel combinations is lacking. Phase I-III adult combination clinical trials (≥ 1 drug was immunotherapy; anti-PD-1, PD-L1, or CTLA-4) were reviewed (PubMed Jan 1, 2010 to Sep 1, 2016; ASCO 2014-2016, ASH/ESMO 2014-2015 abstracts). The safe dose for each drug used in each combination was divided by the single-agent recommended dose to calculate dose percentage. Additive dose percentage was the sum of each dose percentage...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28920002/ep4-antagonism-by-e7046-diminishes-myeloid-immunosuppression-and-synergizes-with-treg-reducing-il-2-diphtheria-toxin-fusion-protein-in-restoring-anti-tumor-immunity
#8
Diana I Albu, Zichun Wang, Kuan-Chun Huang, Jiayi Wu, Natalie Twine, Sarah Leacu, Christy Ingersoll, Lana Parent, Winnie Lee, Diana Liu, Renee Wright-Michaud, Namita Kumar, Galina Kuznetsov, Qian Chen, Wanjun Zheng, Kenichi Nomoto, Mary Woodall-Jappe, Xingfeng Bao
Reprogramming of immunosuppressive tumor microenvironment (TME) by targeting alternatively activated tumor associated macrophages (M2TAM), myeloid-derived suppressor cells (MDSC), and regulatory T cells (Tregs), represents a promising strategy for developing novel cancer immunotherapy. Prostaglandin E2 (PGE2), an arachidonic acid pathway metabolite and mediator of chronic inflammation, has emerged as a powerful immunosuppressor in the TME through engagement with one or more of its 4 receptors (EP1-EP4). We have developed E7046, an orally bioavailable EP4-specific antagonist and show here that E7046 has specific and potent inhibitory activity on PGE2-mediated pro-tumor myeloid cell differentiation and activation...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28920000/oncolytic-peptide-ltx-315-induces-an-immune-mediated-abscopal-effect-in-a-rat-sarcoma-model
#9
Janne Nestvold, Meng-Yu Wang, Ketil A Camilio, Severin Zinöcker, Torunn Elisabeth Tjelle, Alf Lindberg, Bengt Erik Haug, Gunnar Kvalheim, Baldur Sveinbjørnsson, Øystein Rekdal
LTX 315 is an oncolytic peptide with potent immunological properties. In the present study, we demonstrate that intratumoral treatment with LTX-315 resulted in a complete regression and systemic immune response in a rat fibrosarcoma model. The treatment was T-cell dependent, and also resulted in an abscopal effect as demonstrated by the regression of distal non-treated lesions. Significant infiltration of CD8(+) T cells was observed in both treated and non-treated lesions, as shown by immunohistochemical and flow cytometric analysis...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919991/umbilical-cord-blood-cd34-progenitor-derived-nk-cells-efficiently-kill-ovarian-cancer-spheroids-and-intraperitoneal-tumors-in-nod-scid-il2rg-null-mice
#10
Janneke S Hoogstad-van Evert, Jeannette Cany, Dirk van den Brand, Manon Oudenampsen, Roland Brock, Ruurd Torensma, Ruud L Bekkers, Joop H Jansen, Leon F Massuger, Harry Dolstra
Adoptive transfer of allogeneic natural killer (NK) cells is an attractive therapy approach against ovarian carcinoma. Here, we evaluated the potency of highly active NK cells derived from human CD34+ haematopoietic stem and progenitor cells (HSPC) to infiltrate and mediate killing of human ovarian cancer spheroids using an in vivo-like model system and mouse xenograft model. These CD56+Perforin+ HSPC-NK cells were generated under stroma-free conditions in the presence of StemRegenin-1, IL-15, and IL-12, and exerted efficient cytolytic activity and IFNγ production toward ovarian cancer monolayer cultures...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919988/identification-of-a-hla-a-0201-restricted-immunogenic-epitope-from-the-universal-tumor-antigen-depdc1
#11
Anna Tosi, Silvia Dalla Santa, Elisa Cappuzzello, Carolina Marotta, Dawid Walerich, Giannino Del Sal, Paola Zanovello, Roberta Sommaggio, Antonio Rosato
The identification of universal tumor-specific antigens shared between multiple patients and/or multiple tumors is of great importance to overcome the practical limitations of personalized cancer immunotherapy. Recent studies support the involvement of DEPDC1 in many aspects of cancer traits, such as cell proliferation, resistance to induction of apoptosis and cell invasion, suggesting that it may play key roles in the oncogenic process. In this study, we report that DEPDC1 expression is upregulated in most types of human tumors, and closely linked to a poorer prognosis; therefore, it might be regarded as a novel universal oncoantigen potentially suitable for targeting many different cancers...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919895/mind-the-gaps-in-tumor-immunity-impact-of-connexin-mediated-intercellular-connections
#12
REVIEW
María Alejandra Gleisner, Mariela Navarrete, Francisca Hofmann, Flavio Salazar-Onfray, Andrés Tittarelli
Gap junctions (GJs)-mediated intercellular communications (GJICs) are connexin (Cx)-formed plasma membrane channels that allow for the passage of small molecules between adjacent cells, and are involved in several physiopathological processes, including immune responses against cancer. In general, tumor cells are poorly coupled through GJs, mainly due to low Cx expression or reduced channel activity, suggesting that Cxs may have tumor suppressor roles. However, more recent data indicate that Cxs and/or GJICs may also in some cases promote tumor progression...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28919894/potentiation-of-natural-killer-cells-for-cancer-immunotherapy-a-review-of-literature
#13
REVIEW
Lacy E Lowry, William A Zehring
It is widely acknowledged that the human immune system plays a crucial role in preventing the formation and progression of innumerable types of cancer (1). The mechanisms by which this occurs are numerous, including contributions from both the innate and adaptive immune systems. As such, immunotherapy has long been believed to be an auspicious solution in the treatment of malignancy (2). Recent research has highlighted the promise of natural killer (NK) cells as a more directed immunotherapy approach. This paper will focus on the methods of potentiation of NK cells for their use in cancer therapy...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28919785/biomarker-analysis-and-clinical-relevance-of-tk1-on-the-cell-membrane-of-burkitt-s-lymphoma-and-acute-lymphoblastic-leukemia
#14
Evita G Weagel, Wei Meng, Michelle H Townsend, Edwin J Velazquez, Rachel A Brog, Michael W Boyer, K Scott Weber, Richard A Robison, Kim L O'Neill
TK1 is an enzyme involved in DNA synthesis and repair. TK1 is usually found elevated in cancer patients' serum, which makes it a useful tumor proliferation biomarker that strongly correlates with cancer stage, metastatic capabilities, and recurrence risk. In this study, we show that TK1 is upregulated and localizes on the plasma membrane of Burkitt's lymphoma, acute promyelocytic leukemia, T cell leukemia, and acute lymphoblastic leukemia (ALL). Using flow cytometry, we confirmed that TK1 localizes on the surface of Raji, HL60, and Jurkat cell lines and on ALL clinical samples...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28919783/toll-like-receptors-7-and-8-expression-correlates-with-the-expression-of-immune-biomarkers-and-positively-predicts-the-clinical-outcome-of-patients-with-melanoma
#15
Moucheng Zhang, Zhilong Yan, Junjiang Wang, Xueqing Yao
BACKGROUND: Toll-like receptors (TLRs) play a critical role in cancer, yet the clinical relevance of TLR7/8 expression in melanoma remains unclear. This study aimed to evaluate the prognostic value of TLR7/8 mRNA levels in melanoma and their correlation with immune biomarkers relevant to disease progression. METHODS: Normalized gene expression and corresponding clinical data of patients with skin cutaneous melanoma were obtained from two public databases: the Cancer Genome Atlas and GSE19234...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28919484/lung-cancer-epigenetics-from-knowledge-to-applications
#16
REVIEW
Michaël Duruisseaux, Manel Esteller
Lung cancer is the leading cause of cancer-related mortality worldwide. Advances in our understanding of the genomics of lung cancer have led to substantial progress in the treatment of specific molecular subsets. Immunotherapy also emerges as a major breakthrough in lung cancer treatment. However, challenges remain as a consensual approach for early lung cancer detection remains elusive while primary or secondary drug resistance eventually leads to treatment failure in all patients with advanced disease. Furthermore, a large portion of patients are still treated with conventional chemotherapy that is only modestly effective...
September 14, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28919454/a-robust-immune-system-conditions-the-response-to-abagovomab-anti-idiotypic-monoclonal-antibody-mimicking-the-ca125-protein-vaccination-in-ovarian-cancer-patients
#17
Alessandra Battaglia, Marco Fossati, Alexia Buzzonetti, Giovanni Scambia, Andrea Fattorossi
INTRODUCTION: Despite encouraging phase I and II study results, vaccination of ovarian cancer patients with abagovomab - an anti-idiotypic mAb that mimics the ovarian cancer CA125 protein - failed to demonstrate efficacy in the phase III trial named MIMOSA (NCT00418574). We postulated that in this trial patients with a more robust immune system did respond to abagovomab but went undetected among a larger number of non-responders. We also postulated that assessment of the immune system status ahead of abagovomab administration might predict patients' propensity to respond to abagovomab...
September 14, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28918542/current-chemotherapeutic-regimens-for-brain-metastases-treatment
#18
Joo Yeon Nam, Barbara J O'Brien
Brain metastasis is a common complication in advanced systemic cancer, with an increasing incidence. The diagnosis of brain metastasis historically portended a dismal prognosis. The successful development of effective treatments for patients with brain metastasis is complicated by the differences among cancer subtypes, the limited understanding of the underlying pathophysiology of BM, the impact of the blood-brain barrier, and other factors. There is now renewed interest in treating this often devastating complication of cancer, and in understanding the underlying mechanisms of disease in this "sanctuary" site...
September 16, 2017: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/28918429/synergy-of-dendritic-cell-vaccines-and-avasimibe-in-treatment-of-head-and-neck-cancer-in-mice
#19
Xin Chen, Qibin Song, Leiming Xia, Ximing Xu
BACKGROUND The main purpose of this study was to explore the antitumor effect and mechanisms of ACAT1 inhibitor combined with CSCs-DC vaccine. MATERIAL AND METHODS We isolated HNSCC CSCs and gained CSCs antigens, then used CSCs antigens to load dendritic cells (DC) and generated a CSCs-DC vaccine. We treated mice after surgical excision of established SCC7 tumors with CSCs-DC vaccine and/or ACAT1 inhibitor, and recorded local tumor relapse and host survival. T cells and B cells were harvested from mice treated with CSCs-DC vaccine and/or ACAT1 inhibitor...
September 17, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28918263/dna-nanotechnology-based-composite-type-gold-nanoparticle-immunostimulatory-dna-hydrogel-for-tumor-photothermal-immunotherapy
#20
Tomoya Yata, Yuki Takahashi, Mengmeng Tan, Hirotaka Nakatsuji, Shozo Ohtsuki, Tatsuya Murakami, Hiroshi Imahori, Yuka Umeki, Tomoki Shiomi, Yoshinobu Takakura, Makiya Nishikawa
Success of tumor photothermal immunotherapy requires a system that induces heat stress in cancer cells and enhances strong anti-tumor immune responses. Here, we designed a composite-type immunostimulatory DNA hydrogel consisting of a hexapod-like structured DNA (hexapodna) with CpG sequences and gold nanoparticles. Mixing of the properly designed hexapodna and oligodeoxynucleotide-modified gold nanoparticles resulted in the formation of composite-type gold nanoparticle-DNA hydrogels. Laser irradiation of the hydrogel resulted in the release of hexapodna, which efficiently stimulated immune cells to release proinflammatory cytokines...
September 9, 2017: Biomaterials
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