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immune mediated metastasis

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https://www.readbyqxmd.com/read/28634284/co-administration-of-rankl-and-ctla4-antibodies-enhances-lymphocyte-mediated-anti-tumor-immunity-in-mice
#1
Elizabeth Ahern, Heidi Harjunpaa, Deborah Barkauskas, Stacey Allen, Kazuyoshi Takeda, Hideo Yagita, David Wyld, William C Dougall, Michele W L Teng, Mark J Smyth
Purpose: Novel partners for established immune checkpoint inhibitors in the treatment of cancer are needed to address the problems of primary and acquired resistance. The efficacy of combination RANKL and CTLA4 blockade in anti-tumor immunity has been suggested by recent case reports in melanoma. Here we provide a rationale for this combination in mouse models of cancer. <br />Experimental Design: The efficacy and mechanism of a combination of RANKL and CTLA4 blockade was examined by tumor infiltrating lymphocyte analysis, tumor growth and metastasis using a variety of neutralizing antibodies and gene-targeted mice...
June 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28633645/generation-of-populations-of-antigen-specific-cytotoxic-t-cells-using-dcs-transfected-with-dna-construct-encoding-her2-neu-tumor-antigen-epitopes
#2
Maria Kuznetsova, Julia Lopatnikova, Julia Khantakova, Rinat Maksyutov, Amir Maksyutov, Sergey Sennikov
BACKGROUND: Recent fundamental and clinical studies have confirmed the effectiveness of utilizing the potential of the immune system to remove tumor cells disseminated in a patient's body. Cytotoxic T lymphocytes (CTLs) are considered the main effectors in cell-mediated antitumor immunity. Approaches based on antigen presentation to CTLs by dendritic cells (DCs) are currently being intensively studied, because DCs are more efficient in tumor antigen presentation to T cells through their initiation of strong specific antitumor immune responses than other types of antigen-presenting cells...
June 20, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28627679/exosomes-new-players-in-cancer-review
#3
Wei Guo, Yibo Gao, Ning Li, Fei Shao, Chunni Wang, Pan Wang, Zhenlin Yang, Renda Li, Jie He
The past decade has witnessed an exponential increase in research on exosomes. For many years considered to be extracellular debris, exosomes are now considered important mediators in intercellular communication. The capability of exosomes to transfer proteins, DNA, mRNA, as well as non-coding RNAs has made them an attractive focus of research into the pathogenesis of different diseases, including cancer. Increasing evidence suggests that tumor cells release a large sum of exosomes, which may not only influence proximal tumor cells and stromal cells in local microenvironment, but also can exert systemic effects when participating in blood circulation...
June 13, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28617999/adenosine-an-endogenous-mediator-in-the-pathogenesis-of-gynecological-cancer
#4
REVIEW
Amirhossein Bahreyni, Seyed Sattar Samani, Elnaz Ghorbani, Farzad Rahmani, Reza Khayami, Younes Toroghian, Reihane Behnam-Rassouli, Majid Khazaei, Mikhail Ryzhikov, Mohammad Reza Parizadeh, Malihe Hasanzadeh, Amir Avan, Seyed Mahdi Hassanian
Extracellular concentration of adenosine increases in the hypoxic tumor microenvironment. Adenosine signaling regulates apoptosis, angiogenesis, metastasis and immune suppression in cancer cells. Adenosine-induced cell responses depend upon different subtypes of adenosine receptors activation and type of cancer. Suppression of adenosine signaling via inhibition of adenosine receptors or adenosine generating enzymes including CD39 and CD73 on ovarian or cervical cancer cells is a potentially novel therapeutic approach for gynecological cancer patients...
June 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28611041/an-immunosuppressive-dendritic-cell-subset-accumulates-at-secondary-sites-and-promotes-metastasis-in-pancreatic-cancer
#5
Justin A Kenkel, William W Tseng, Matthew G Davidson, Lorna Tolentino, Okmi Choi, Nupur Bhattacharya, E Scott Seeley, Daniel Winer, Nathan E Reticker-Flynn, Edgar G Engleman
Pancreatic ductal adenocarcinoma (PDAC) after complete surgical resection is often followed by distant metastatic relapse for reasons that remain unclear. In this study, we investigated how the immune response at secondary sites affects tumor spread in murine models of metastatic PDAC. Early metastases were associated with dense networks of CD11b(+)CD11c(+)MHC-II(+)CD24(+)CD64(low)F4/80(low) dendritic cells (DC), which developed from monocytes in response to tumor-released GM-CSF. These cells uniquely expressed MGL2 and PD-L2 in the metastatic microenvironment and preferentially induced the expansion of T regulatory cells (Treg) in vitro and in vivo...
June 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28609459/het0016-decreases-lung-metastasis-from-breast-cancer-in-immune-competent-mouse-model
#6
Thaiz F Borin, Adarsh Shankar, Kartik Angara, Mohammad H Rashid, Meenu Jain, Asm Iskander, Roxan Ara, Iryna Lebedyeva, Hasan Korkaya, Bhagelu R Achyut, Ali S Arbab
Distant metastasis is the primary cause of death in the majority of the cancer types. Recently, much importance has been given to tumor microenvironment (TME) in the development of invasive malignant tumors, as well as the metastasis potential. The ability of tumor cells to modulate TME and to escape immune-mediated attack by releasing immunosuppressive cytokines has become a hallmark of breast cancer. Our study shows the effect of IV formulation of HET0016 (HPßCD-HET0016) a selective inhibitor of 20-HETE synthesis, administered intravenously in immune-competent in vivo mouse model of murine breast cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28601064/types-of-immune-inflammatory-responses-as-a-reflection-of-cell-cell-interactions-under-conditions-of-tissue-regeneration-and-tumor-growth
#7
REVIEW
L A Tashireva, V M Perelmuter, V N Manskikh, E V Denisov, O E Savelieva, E V Kaygorodova, M V Zavyalova
Inflammatory infiltration of tumor stroma is an integral reflection of reactions that develop in response to any damage to tumor cells including immune responses to antigens or necrosis caused by vascular disorders. In this review, we use the term "immune-inflammatory response" (IIR) that allows us to give an integral assessment of the cellular composition of the tumor microenvironment. Two main types of IIRs are discussed: type 1 and 2 T-helper reactions (Th1 and Th2), as well as their inducers: immunosuppressive responses and reactions mediated by Th22 and Th17 lymphocytes and capable of modifying the main types of IIRs...
May 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28600225/b7-h4-is-a-prognostic-biomarker-for-poor-survival-in-patients-with-pancreatic-cancer
#8
Lingwei Shen, Yun Qian, Weigen Wu, Tianhao Weng, Frederick X C Wang, Bo Hong, Zhigang Wu, Qi Wang, Yiwen Sang, Hong Zhang, Xinhui Zhou, Hangping Yao
B7-H4 belongs to the immune costimulatory B7 family and is thought to negatively regulate T-cell mediated immunity, and may contribute an important role in tumor immune evasion. Although the expression of B7-H4 has been observed in human pancreatic cancer, the prognostic significance of this expression is poorly understood. This present study explored the prognostic value of B7-H4 in pancreatic cancer. Patients with pancreatic cancer and healthy controls were recruited at the Second Affiliated Hospital to Zhejiang University from January 2011 to December 2014...
June 6, 2017: Human Pathology
https://www.readbyqxmd.com/read/28590012/swiprosin-1-its-expression-and-diverse-biological-functions
#9
Ramesh P Thylur, Raghavendra Gowda, Sumita Mishra, Chang-Duk Jun
Swiprosin-1/EFhd2 is a Ca(2+) binding adapter protein involved in the various cellular functions. Swiprosin-1 is significantly upregulated in a number of pathological conditions of inflammation, neurodegeneration, and cancer. Swiprosin-1 associated with actin and its expression level amplifies the production of proinflammatory mediators and modulates the activation of transcription factor during immune cells activation. This review aims at providing an overview of the expression and function of swiprosin-1/EFhd2 in various pathophysiological conditions...
June 7, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28589318/matricellular-proteins-in-cancer-a-focus-on-secreted-frizzled-related-proteins
#10
Krista Marie Vincent, Lynne-Marie Postovit
Tumours are complex entities, wherein cancer cells interact with myriad soluble, insoluble and cell associated factors. These microenvironmental mediators regulate tumour growth, progression and metastasis, and are produced by cancer cells and by stromal components such as fibroblast, adipocytes and immune cells. Through their ability to bind to extracellular matrix proteins, cell surface receptors and growth factors, matricellular proteins enable a dynamic reciprocity between cancer cells and their microenvironment...
June 7, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/28574228/apkc-%C3%AE-p-sp1-snail-signaling-induces-epithelial-mesenchymal-transition-and-immunosuppression-in-cholangiocarcinoma
#11
Yawei Qian, Wei Yao, Tao Yang, Yan Yang, Yan Liu, Qi Shen, Jian Zhang, Weipeng Qi, Jianming Wang
Cholangiocarcinoma (CCA) is a highly malignant bile duct cancer that tends to invade and metastasize early. The epithelial-mesenchymal transition (EMT) has been implicated in cancer cell invasion and metastasis, as well as in cancer cell evasion of host immunity. In this study, we investigated the interaction between atypical protein kinase C-iota (aPKC-ι) and Snail in the regulation of EMT and its relationship to CCA immunosuppression. Our results demonstrated that aPKC-ι, Snail, and infiltrated immunosuppressive cells were significantly up-regulated in CCA tumor tissues and were linked to poor prognosis...
June 2, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28560327/antibody-mediated-neutralization-of-soluble-mic-significantly-enhances-ctla4-blockade-therapy
#12
Jingyu Zhang, Dai Liu, Guangfu Li, Kevin F Staveley-O'Carroll, Julie N Graff, Zihai Li, Jennifer D Wu
Antibody therapy targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA4) elicited survival benefits in cancer patients; however, the overall response rate is limited. In addition, anti-CTLA4 antibody therapy induces a high rate of immune-related adverse events. The underlying factors that may influence anti-CTLA4 antibody therapy are not well defined. We report the impact of a cancer-derived immune modulator, the human-soluble natural killer group 2D (NKG2D) ligand sMIC (soluble major histocompatibility complex I chain-related molecule), on the therapeutic outcome of anti-CTLA4 antibody using an MIC transgenic spontaneous TRAMP (transgenic adenocarcinoma of the mouse prostate)/MIC tumor model...
May 2017: Science Advances
https://www.readbyqxmd.com/read/28542406/human-igg3-with-extended-half-life-does-not-improve-fc-gamma-receptor-mediated-cancer-antibody-therapies-in-mice
#13
Rens Braster, Simran Grewal, Remco Visser, Helga K Einarsdottir, Marjolein van Egmond, Gestur Vidarsson, Marijn Bögels
BACKGROUND: Current anti-cancer therapeutic antibodies that are used in the clinic are predominantly humanized or fully human immunoglobulin G1 (IgG1). These antibodies bind with high affinity to the target antigen and are efficient in activating the immune system via IgG Fc receptors and/or complement. In addition to IgG1, three more isotypes are present in humans, of which IgG3 has been found to be superior compared to human IgG1 in inducing antibody dependent cell cytotoxicity (ADCC), phagocytosis or activation of complement in some models...
2017: PloS One
https://www.readbyqxmd.com/read/28539553/identification-of-cancer-stem-cell-antigens-and-development-of-ctl-mediated-cancer-immunotherapy
#14
Sho Miyamoto, Takayuki Kanaseki, Yoshihiko Hirohashi, Tomohide Tsukahara, Yasuhiro Kikuchi, Noriyuki Sato, Toshihiko Torigoe
  Cancer-stem cells (or cancer-stem like cells, CSC) play an indispensable role in tumor initiation or tumor development in vivo. However, CSCs are resistant to conventional therapies including chemo/radiotherapy and a certain molecularly-targeted therapy, thereby are responsible for tumor relapse or metastasis in clinical settings. In this review, we focus on cytotoxic T-cell mediated immune responses against CSCs and discuss a challenge of targeting CSCs as well as the development of CSC-based cancer immunotherapy, which is an emerging and promising strategy toward a complete cure of quite a few types of cancers...
2017: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28537911/a-novel-immunotherapy-targeting-mmp-14-limits-hypoxia-immune-suppression-and-metastasis-in-triple-negative-breast-cancer-models
#15
Binbing Ling, Kathleen Watt, Sunandan Banerjee, Daniel Newsted, Peter Truesdell, Jarrett Adams, Sachdev S Sidhu, Andrew Wb Craig
Matrix metalloproteinase-14 (MMP-14) is a clinically relevant target in metastatic cancers due to its role in tumor progression and metastasis. Since active MMP-14 is localized on the cell surface, it is amenable to antibody-mediated blockade in cancer, and here we describe our efforts to develop novel inhibitory anti-MMP-14 antibodies. A phage-displayed synthetic humanized Fab library was screened against the extracellular domain of MMP-14 and a panel of MMP14-specific Fabs were identified. A lead antibody that inhibits the catalytic domain of MMP-14 (Fab 3369) was identified and treatment of MDA-MB-231 breast cancer cells with Fab 3369 led to significant loss of extracellular matrix degradation and cell invasion abilities...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28536330/-exosomes-and-immune-cells
#16
Naohiro Seo
In addition to the cytokines and cytotoxic granules, exosomes have been known as the intercellular communicator and cytotoxic missile of immune cells for the past decade. It has been well known that mature dendritic cell(DC)-derived exosomes participate in the T cell and natural killer(NK)cell activation, while immature DCs secrete tolerogenic exosomes for regulatory T(Treg)cell generation. Treg cell-derived EVs act as a suppressor against pathogenic type-1 T helper(Th1)cell responses. CD8+ T cells produce tumoricidal exosomes for preventing tumor invasion and metastasis transiently after T cell receptor(TCR)-mediated stimulation...
May 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28506076/nos2-as-an-emergent-player-in-progression-of-cancer
#17
Douglas D Thomas, David A Wink
Although the inducible form of nitric oxide synthase (NOS2) was initially shown to be a major player as an antitumor component of the immune response, more recent data have shown that NOS2 expression in cancer cells often predicts poor outcome. Unlike growth factors associated with a single oncogenic pathway, nitric oxide (NO) has a ubiquitous nature wherein it simultaneously mediates major oncogenic pathways from Akt/PI3K and RAS/ERK to HIF1a and TGFb. These interactive loops perpetuate oncogenic mechanism that leads to increased cancer stemness, proliferation metastasis, chemoresistance, angiogenesis, and immunosuppression...
June 10, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28496107/cd163-cd204-tumor-associated-macrophages-contribute-to-t-cell-regulation-via-interleukin-10-and-pd-l1-production-in-oral-squamous-cell-carcinoma
#18
Keigo Kubota, Masafumi Moriyama, Sachiko Furukawa, Haque A S M Rafiul, Yasuyuki Maruse, Teppei Jinno, Akihiko Tanaka, Miho Ohta, Noriko Ishiguro, Masaaki Yamauchi, Mizuki Sakamoto, Takashi Maehara, Jun-Nosuke Hayashida, Shintaro Kawano, Tamotsu Kiyoshima, Seiji Nakamura
Tumor-associated macrophages (TAMs) promote cancer cell proliferation, invasion, and metastasis by producing various mediators. Although preclinical studies demonstrated that TAMs preferentially express CD163 and CD204, the TAM subsets in oral squamous cell carcinoma (OSCC) remain unknown. In this study, we examined the expression and role of TAM subsets in OSCC. Forty-six patients with OSCC were analyzed for expression of TAMs in biopsy samples by immunohistochemistry. We examined TAM subsets and their production of immune suppressive molecules (IL-10 and PD-L1) in peripheral blood mononuclear cells from three OSCC patients by flow cytometry...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28476944/impact-of-age-on-outcomes-with-immunotherapy-for-patients-with-melanoma
#19
Allison S Betof, Ryan D Nipp, Anita Giobbie-Hurder, Romany A N Johnpulle, Krista Rubin, Samuel M Rubinstein, Keith T Flaherty, Donald P Lawrence, Douglas B Johnson, Ryan J Sullivan
BACKGROUND: Monoclonal antibodies (mAb) targeting PD-1/PD-L1 have revolutionized melanoma treatment, yet data regarding effectiveness and tolerability across age groups is limited. We sought to determine the impact of age on overall survival (OS), progression-free survival (PFS), and rates of immune-mediated toxicities in patients treated with anti-PD-1/anti-PD-L1 mAb at two academic medical centers. METHODS: We retrospectively collected data on all patients with metastatic melanoma treated with anti-PD-1/PD-L1 mAb between May 2009 and April 2015...
May 5, 2017: Oncologist
https://www.readbyqxmd.com/read/28466296/t-independent-response-mediated-by-oncolytic-tanapoxvirus-recombinants-expressing-interleukin-2-and-monocyte-chemoattractant-protein-1-suppresses-human-triple-negative-breast-tumors
#20
Yogesh R Suryawanashi, Tiantian Zhang, Helene M Woyczesczyk, John Christie, Emily Byers, Steven Kohler, Robert Eversole, Charles Mackenzie, Karim Essani
Human triple negative breast cancer (TNBC) is an aggressive disease, associated with a high rate of recurrence and metastasis. Current therapeutics for TNBC are limited, highly toxic and show inconsistent efficacy due to a high degree of intra-tumoral and inter-tumoral heterogeneity. Oncolytic viruses (OVs) are an emerging treatment option for cancers. Several OVs are currently under investigation in preclinical and clinical settings. Here, we examine the oncolytic potential of two tanapoxvirus (TPV) recombinants expressing mouse monocyte chemoattractant protein (mMCP)-1 [also known as mCCL2] and mouse interleukin (mIL)-2, in human TNBC, in vitro and in vivo...
June 2017: Medical Oncology
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