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cancer cell,tumor,immune surveilance

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https://www.readbyqxmd.com/read/28932842/microfluidic-isolation-of-platelet-covered-circulating-tumor-cells
#1
Xiaocheng Jiang, Keith H K Wong, Aimal H Khankhel, Mahnaz Zeinali, Eduardo Reategui, Matthew J Phillips, Xi Luo, Nicola Aceto, Fabio Fachin, Anh N Hoang, Wooseok Kim, Annie E Jensen, Lecia V Sequist, Shyamala Maheswaran, Daniel A Haber, Shannon L Stott, Mehmet Toner
The interplay between platelets and tumor cells is known to play important roles in metastasis by enhancing tumor cell survival, tumor-vascular interactions, and escape from immune surveillance. However, platelet-covered circulating tumor cells (CTC) are extremely difficult to isolate due to masking or downregulation of surface epitopes. Here we describe a microfluidic platform that takes advantage of the satellite platelets on the surface of these "stealth" CTCs as a ubiquitous surface marker for isolation...
September 21, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28932639/soluble-nkg2d-ligands-in-the-ovarian-cancer-microenvironment-are-associated-with-an-adverse-clinical-outcome-and-decreased-memory-effector-t-cells-independent-of-nkg2d-downregulation
#2
Maulik Vyas, Silke Reinartz, Nathalie Hoffmann, Katrin S Reiners, Sonja Lieber, Julia M Jansen, Uwe Wagner, Rolf Müller, Elke Pogge von Strandmann
The immune receptor NKG2D is predominantly expressed on NK cells and T cell subsets and confers anti-tumor activity. According to the current paradigm, immune surveillance is counteracted by soluble ligands shed into the microenvironment, which down-regulate NKG2D receptor expression. Here, we analyzed the clinical significance of the soluble NKG2D ligands sMICA and sULBP2 in the malignancy-associated ascites of ovarian cancer. We show that high levels of sMICA and sULBP2 in ascites were associated with a poor prognosis...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28928833/disrupted-fibroblastic-reticular-cells-and-interleukin-7-expression-in-tumor-draining-lymph-nodes
#3
Jianbao Gao, Lintao Zhao, Lina Liu, Yang Yang, Bo Guo, Bo Zhu
The immune system of patients with cancer is usually in an inhibitory state. Lymph node (LN) draining of pathological sites provides a suitable microenvironment where adaptive immune responses mainly occur. However, the microenvironment in the tumor draining lymph nodes (TDLNs) of patients with cancer appears to be in favor of tolerance. The effects of tumor cells on TDLNs have not been elaborated clearly. The present results have indicated that tumor cells may directly affect TDLNs by decreasing the fibroblastic reticular cell population that led to less interleukin-7 secretion...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28924054/immunosurveillance-and-immunoediting-of-breast-cancer-via-class-i-mhc-receptors
#4
Megan M Tu, Mir Munir A Rahim, Celine Sayed, Ahmad Bakur Mahmoud, Andrew P Makrigiannis
Ly49 receptors, which recognize 'self' class I major histocompatibility complex (MHC-I) molecules, enable natural killer (NK) cells to detect loss of MHC-I expression on transformed and virally-infected cells. The impact of NK cell-mediated MHC-I surveillance on immunoediting of breast cancer is still not fully understood. This work assesses the impact of Ly49 receptors on tumor development in terms of cancer control and in driving immune-evading cancer mutations. Genetically modified Ly49-deficient mice and those lacking NK cells through antibody depletion were less able to control E0771-derived mammary tumors in an MHC-I-dependent fashion...
September 18, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28923860/in-silico-modeling-of-immunotherapy-and-stroma-targeting-therapies-in-human-colorectal-cancer
#5
Jakob Nikolas Kather, Jan Poleszczuk, Meggy Suarez-Carmona, Johannes Krisam, Pornpimol Charoentong, Nektarios A Valous, Cleo-Aron Weis, Luca Tavernar, Florian Leiss, Esther Herpel, Fee Klupp, Alexis Ulrich, Martin Schneider, Alexander Marx, Dirk Jaeger, Niels Halama
Despite the fact that the local immunological microenvironment shapes the prognosis of colorectal cancer, immunotherapy has shown no benefit for the vast majority of colorectal cancer patients. A better understanding of the complex immunological interplay within the microenvironment is required. In this study, we utilized wet lab migration experiments and quantitative histological data of human colorectal cancer tissue samples (n=20) including tumor cells, lymphocytes, stroma and necrosis to generate a multi-agent spatial model...
September 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28919706/profile-of-pembrolizumab-in-the-treatment-of-head-and-neck-squamous-cell-carcinoma-design-development-and-place-in-therapy
#6
REVIEW
Sulsal Haque, Mahender Yellu, Jaskirat Randhawa, Nooshin Hashemi-Sadraei
Head and neck squamous cell cancer (HNSCC) is the sixth most common malignancy worldwide, and despite advances in cytotoxic, surgical and radiation techniques, outcomes are still poor in those with both locally advanced and metastatic diseases. The need for development of better therapeutics along with a greater understanding of the relationship between the immune system and malignancies has led to a new therapeutic modality, immune modulators, particularly checkpoint inhibitors in HNSCC. It is now well recognized that HNSCC circumvents crucial pathways utilized by the immune system to escape surveillance...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28894087/hypoxia-inducible-factor-hif-1-promotes-myeloid-derived-suppressor-cells-accumulation-through-entpd2-cd39l1-in-hepatocellular-carcinoma
#7
David Kung-Chun Chiu, Aki Pui-Wah Tse, Iris Ming-Jing Xu, Jane Di Cui, Robin Kit-Ho Lai, Lynna Lan Li, Hui-Yu Koh, Felice Ho-Ching Tsang, Larry Lai Wei, Chun-Ming Wong, Irene Oi-Lin Ng, Carmen Chak-Lui Wong
Myeloid-derived suppressor cells (MDSCs) possess immunosuppressive activities, which allow cancers to escape immune surveillance and become non-responsive to immune checkpoints blockade. Here we report hypoxia as a cause of MDSC accumulation. Using hepatocellular carcinoma (HCC) as a cancer model, we show that hypoxia, through stabilization of hypoxia-inducible factor-1 (HIF-1), induces ectoenzyme, ectonucleoside triphosphate diphosphohydrolase 2 (ENTPD2/CD39L1), in cancer cells, causing its overexpression in HCC clinical specimens...
September 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28891811/nf-%C3%AE%C2%BAb-regulates-gdf-15-to-suppress-macrophage-surveillance-during-early-tumor-development
#8
Nivedita M Ratnam, Jennifer M Peterson, Erin E Talbert, Katherine J Ladner, Priyani V Rajasekera, Carl R Schmidt, Mary E Dillhoff, Benjamin J Swanson, Ericka Haverick, Raleigh D Kladney, Terence M Williams, Gustavo W Leone, David J Wang, Denis C Guttridge
Macrophages are attracted to developing tumors and can participate in immune surveillance to eliminate neoplastic cells. In response, neoplastic cells utilize NF-κB to suppress this killing activity, but the mechanisms underlying their self-protection remain unclear. Here, we report that this dynamic interaction between tumor cells and macrophages is integrally linked by a soluble factor identified as growth and differentiation factor 15 (GDF-15). In vitro, tumor-derived GDF-15 signals in macrophages to suppress their proapoptotic activity by inhibiting TNF and nitric oxide (NO) production...
September 11, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28888577/crispr-knock-out-ctla-4-enhances-the-anti-tumor-activity-of-cytotoxic-t-lymphocytes
#9
Long Shi, Tongyu Meng, Zhilong Zhao, Jinsheng Han, Wei Zhang, Fei Gao, Jianhui Cai
T cell-mediated anti-tumor immunity plays a pivotal role in cancer immune surveillance. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a protein receptor mainly expressed in activated T cells and regulatory T cells. CTLA-4 competes with CD28 for ligand binding and generates inhibitory signals to attenuate T cell activation. The blockade of CTLA-4 mediated immune inhibitory checkpoint has been associated with enhanced anti-tumor immunity. In this study, we use CRISPR-Cas9 system to knock out (KO) CTLA-4 from cytotoxic T lymphocytes (CTLs) and evaluate its effect on the anti-tumor activity of the CTLs...
September 6, 2017: Gene
https://www.readbyqxmd.com/read/28882998/transplantation-of-ips-derived-tumor-cells-with-a-homozygous-mhc-haplotype-induces-grp94-antibody-production-in-mhc-matched-macaques
#10
Hirohito Ishigaki, Toshinaga Maeda, Hirokazu Inoue, Tsuyoshi Akagi, Takako Sasamura, Hideaki Ishida, Toshiro Inubushi, Junko Okahara, Takashi Shiina, Misako Nakayama, Yasushi Itoh, Kazumasa Ogasawara
Immune surveillance is a critical component of the anti-tumor response in vivo, yet the specific components of the immune system involved in this regulatory response remain unclear. In this study, we demonstrate that autoantibodies can mitigate tumor growth in vitro and in vivo. We generated two cancer cell lines, embryonal carcinoma and glioblastoma cell lines, from monkey induced pluripotent stem cells (iPSC) carrying a homozygous haplotype of major histocompatibility complex (MHC, Mafa in Macaca fascicularis)...
September 7, 2017: Cancer Research
https://www.readbyqxmd.com/read/28881816/autophagy-related-genes-are-induced-by-histone-deacetylase-inhibitor-suberoylanilide-hydroxamic-acid-via-the-activation-of-cathepsin-b-in-human-breast-cancer-cells
#11
Han Han, Jing Li, Xiuyan Feng, Hui Zhou, Shanchun Guo, Weiqiang Zhou
Autophagy is involved in modulating tumor cell motility and invasion, resistance to epithelial-to-mesenchymal transition, anoikis, and escape from immune surveillance. We have previous shown that SAHA is capable to induce several apoptosis and autophagy-related gene expression in breast cancers. However, the exact mechanisms of autophagy activation in this context have not been fully identified. Our results showed that the expression and the activity of Cathepsin B (CTSB), one of the major lysosomal cysteine proteases, were significantly increased in MDA-MB- 231 and MCF-7 cells upon SAHA treatment...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881756/mm-bmscs-induce-na%C3%A3-ve-cd4-t-lymphocytes-dysfunction-through-fibroblast-activation-protein-%C3%AE
#12
Xiaofei Wu, Yadan Wang, Jian Xu, Ting Luo, Jun Deng, Yu Hu
BACKGROUND: The tumor microenvironment plays a major role in multiple myelomas (MM). MM-BMSCs (bone marrow mesenchymal stromal cells) can support tumor growth and immune surveillance escape. On the other hand, fibroblast activation protein α, expressed by cancer stroma cells including BMSCs, has been shown to potentiate epithelial cancers growth and immune suppression. RESULTS: MM-BMSC inhibited proliferation of T cells (P = 0.0138), promoted senescence of T cells (P < 0...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28878676/pd-1-and-pd-l1-checkpoint-signaling-inhibition-for-cancer-immunotherapy-mechanism-combinations-and-clinical-outcome
#13
REVIEW
Hashem O Alsaab, Samaresh Sau, Rami Alzhrani, Katyayani Tatiparti, Ketki Bhise, Sushil K Kashaw, Arun K Iyer
Several cancers are highly refractory to conventional chemotherapy. The survival of tumors in several cases is assisted by checkpoint immunomodulation to maintain the imbalance between immune surveillance and cancer cell proliferation. Check point antibody inhibitors, such as anti-PD-1/PD-L1, are a novel class of inhibitors that function as a tumor suppressing factor via modulation of immune cell-tumor cell interaction. These checkpoint blockers are rapidly becoming a highly promising cancer therapeutic approach that yields remarkable antitumor responses with limited side effects...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28861871/combinatorial-therapies-in-melanoma-mapk-inhibitors-and-beyond
#14
REVIEW
Alice Y Zhou, Douglas B Johnson
Melanoma is the most aggressive of the skin cancers, with historically high rates of morbidity and mortality due to its resistance to traditional cytotoxic therapies. Recently, however, breakthroughs in new therapies have dramatically changed clinical outcomes of this disease. These advances emerged from an improved understanding of tumor oncogenesis and the interacting tumor microenvironment. Small molecules that target the oncogenic mitogen-activated protein kinase (MAPK) pathway, specifically the tyrosine kinase BRAF and its downstream signaling partner MEK, have demonstrated an improved overall survival and progression-free survival for BRAF-mutant melanoma...
August 31, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28859982/role-of-interleukin-il-17-and-t-helper-th-17%C3%A2-cells-in-cancer
#15
Yang Song, Jian Ming Yang
Interleukin-17 (IL-17), a pleiotropic proinflammatory cytokine, is reported to be significantly generated by a distinct subset of CD4(+) T-cells, upgrading cancer-elicited inflammation and preventing cancer cells from immune surveillance. T-helper (Th)17 cells produced from naive CD4(+) T cells have recently been renowned and generally accepted, gaining eminence in cancer studies and playing the effective role in context of cancer. Th17 cells are the main source of IL-17-secreting cells, It was found that other cell types produced this cytokine as well, including Group 3 innate lymphoid cells (ILC3), δγT cells, invariant natural killer T (iNKT) cells, lymphoid-tissue inducer (LTi)-like cells and Natural killer (NK) cells...
August 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28857157/newcastle-disease-virus-mediates-pancreatic-tumor-rejection-via-nk-cell-activation-and-prevents-cancer-relapse-by-prompting-adaptive-immunity
#16
Theresa Schwaiger, Michael R Knittler, Christian Grund, Angela Roemer-Oberdoerfer, Joachim-Friedrich Kapp, Markus M Lerch, Thomas C Mettenleiter, Julia Mayerle, Ulrike Blohm
Pancreatic cancer is the 8(th) most common cause of cancer-related deaths worldwide and the tumor with the poorest prognosis of all solid malignancies. In 1957 it was discovered that Newcastle disease virus (NDV) has oncolytic properties on tumor cells. To study the oncolytic properties of NDV in pancreatic cancer a single dose was administered intravenously in a syngenic orthotopic tumor model employing two different murine pancreatic adenocarcinoma cell lines (DT6606PDA, Panc02). Tumor growth was monitored and immune response was analyzed...
August 31, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28854209/identification-of-a-serum-induced-transcriptional-signature-associated-with-metastatic-cervical-cancer
#17
Anna Palatnik, Shuyun Ye, Christina Kendziorski, Marissa Iden, Jessica S Zigman, Martin J Hessner, Janet S Rader
OBJECTIVE: Tumor cells that escape local tissue control can convert inflammatory cells from tumor suppressors to tumor promoters. Moreover, soluble immune-modulating factors secreted from the tumor environment can be difficult to identify in patient serum due to their low abundance. We used an alternative strategy to infer a metastatic signature induced by sera of cervical cancer patients. METHODS: Sera from patients with local and metastatic cervical cancer were used to induce a disease-specific transcriptional signature in cultured, healthy peripheral blood mononuclear cells (PBMCs)...
2017: PloS One
https://www.readbyqxmd.com/read/28846888/prognostic-value-of-tumor-pd-l1-expression-combined-with-cd8-tumor-infiltrating-lymphocytes-in-high-grade-serous-ovarian-cancer
#18
Qiaohong Wang, Weihua Lou, Wen Di, Xia Wu
Expression of programmed cell death-ligand 1 (PD-L1) is known to be a mechanism whereby cancer can escape immune surveillance, but the relationship between tumor PD-L1 expression and tumor-infiltrating lymphocytes (TILs), and their association with clinical outcomes in patients with high grade serous ovarian cancer (HGSOC) remain ambiguous. We detected the expression of PD-L1 and CD3(+), CD4(+), CD8(+) TILs in 107 patients with HGSOC by immunohistochemical analysis. Using a 5% threshold, 24.30% and 15.89% cases were found with positive expression of PD-L1 in the membrane of tumor cells and TILs respectively...
August 25, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28833116/fatal-myocarditis-following-treatment-with-the-pd-1-inhibitor-nivolumab
#19
Daniel R Matson, Molly A Accola, William M Rehrauer, Robert F Corliss
Therapeutic antibodies targeting the programmed cell death protein 1 (PD-1) pathway function as immune checkpoint inhibitors, allowing the immune system to recognize tumors which otherwise escape immune surveillance. However, these agents can also elicit an autoimmune response by inhibiting the ability of non-neoplastic tissues and regulatory cells to suppress the immune system. Here we present a fatal case of active myocarditis in a 55-year-old man with non-small-cell lung cancer which occurred following monotherapy with the PD-1 inhibitor nivolumab (Opdivo)...
August 17, 2017: Journal of Forensic Sciences
https://www.readbyqxmd.com/read/28826542/cannabinoids-as-anticancer-drugs
#20
Robert Ramer, Burkhard Hinz
The endocannabinoid system encompassing cannabinoid receptors, endogenous receptor ligands (endocannabinoids), as well as enzymes conferring the synthesis and degradation of endocannabinoids has emerged as a considerable target for pharmacotherapeutical approaches of numerous diseases. Besides palliative effects of cannabinoids used in cancer treatment, phytocannabinoids, synthetic agonists, as well as substances that increase endogenous endocannabinoid levels have gained interest as potential agents for systemic cancer treatment...
2017: Advances in Pharmacology
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