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https://www.readbyqxmd.com/read/28651074/chimeric-antigen-receptor-engineered-natural-killer-and-natural-killer-t-cells-for-cancer-immunotherapy
#1
REVIEW
Dominique Bollino, Tonya J Webb
Natural killer (NK) cells of the innate immune system and NK T (NKT) cells, which have roles in both the innate and adaptive responses, are unique lymphocyte subsets that have similarities in their functions and phenotypes. Both cell types can rapidly respond to the presence of tumor cells and participate in immune surveillance and antitumor immune responses. This has incited interest in the development of novel cancer therapeutics based on NK and NKT cell manipulation. Chimeric antigen receptors (CARs), generated through the fusion of an antigen-binding region of a monoclonal antibody or other ligand to intracellular signaling domains, can enhance lymphocyte targeting and activation toward diverse malignancies...
June 9, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28648866/cytokines-in-immunogenic-cell-death-applications-for-cancer-immunotherapy
#2
REVIEW
Anne Showalter, Arati Limaye, Jeremiah L Oyer, Robert Igarashi, Christina Kittipatarin, Alicja J Copik, Annette R Khaled
Despite advances in treatments like chemotherapy and radiotherapy, metastatic cancer remains a leading cause of death for cancer patients. While many chemotherapeutic agents can efficiently eliminate cancer cells, long-term protection against cancer is not achieved and many patients experience cancer recurrence. Mobilizing and stimulating the immune system against tumor cells is one of the most effective ways to protect against cancers that recur and/or metastasize. Activated tumor specific cytotoxic T lymphocytes (CTLs) can seek out and destroy metastatic tumor cells and reduce tumor lesions...
June 22, 2017: Cytokine
https://www.readbyqxmd.com/read/28639898/targeting-interlukin-6-to-relieve-immunosuppression-in-tumor-microenvironment
#3
Qian Liu, Shengnan Yu, Anping Li, Hanxiao Xu, Xinwei Han, Kongming Wu
Immunotolerance is one of the hallmarks of malignant tumors. Tumor cells escape from host immune surveillance through various mechanisms resulting in tumor progression and therapeutic resistance. Interlukin-6 is a proinflammatory cytokine involved in many physiological and pathological processes by integrating with multiple intracellular signaling pathways. Aberrant expression of interlukin-6 is associated with the growth, metastasis, and chemotherapeutic resistance in a wide range of cancers. Interlukin-6 exerts immunosuppressive capacity mostly by stimulating the infiltrations of myeloid-derived suppressor cells, tumor-associated neutrophils, and cancer stem-like cells via Janus-activated kinase/signal transducer and activator of transcription 3 pathway in tumor microenvironment...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28638738/activation-of-the-fcgammareceptoriiia-on-human-natural-killer-cells-leads-to-increased-expression-of-functional-interleukin-21-receptor
#4
Elizabeth L McMichael, Nicholas B Courtney, Megan C Duggan, Robert Wesolowski, Dionisia Quiroga, Sri Vidya Kondadasula, Lakhvir S Atwal, Neela Bhave, Eric Luedke, Alena Cristina Jaime-Ramirez, Amanda R Campbell, Xiaokui Mo, John C Byrd, William E Carson Iii
Natural killer (NK) cells are innate immune effector cells that play a crucial role in immune surveillance and the destruction of cancer cells. NK cells express a low-affinity receptor for the Fc or constant region of immunoglobulin G (FcγRIIIa) and multiple cytokine receptors that respond to antibody-coated targets and cytokines in the tumor microenvironment. In the present work, microarray gene expression analysis revealed that the IL-21 receptor (IL-21R) was strongly upregulated following FcR stimulation...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28638726/downregulation-of-antigen-presentation-associated-pathway-proteins-is-linked-to-poor-outcome-in-triple-negative-breast-cancer-patient-tumors
#5
Martin H Pedersen, Brian L Hood, Hans Christian Beck, Thomas P Conrads, Henrik J Ditzel, Rikke Leth-Larsen
Triple-negative breast cancer (TNBC) is a heterogeneous subtype with varying disease outcomes. Tumor-infiltrating lymphocytes (TILs) are frequent in TNBC and have been shown to correlate with outcome, suggesting an immunogenic component in this subtype. However, other factors intrinsic to the cancer cells may also influence outcome. To identify proteins and molecular pathways associated with recurrence in TNBC, 34 formalin-fixed paraffin-embedded (FFPE) primary TNBC tumors were investigated by global proteomic profiling using mass spectrometry...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28637020/autophagy-related-genes-are-induced-by-histone-deacetylase-inhibitor-suberoylanilide-hydroxamic-acid-via-the-activation-of-cathepsin-b-in-human-breast-cancer-cells
#6
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...
June 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28629173/autophagic-mechanism-in-anti-cancer-immunity-its-pros-and-cons-for-cancer-therapy
#7
REVIEW
Ying-Ying Li, Lynn G Feun, Angkana Thongkum, Chiao-Hui Tu, Shu-Mei Chen, Medhi Wangpaichitr, Chunjing Wu, Macus T Kuo, Niramol Savaraj
Autophagy, a self-eating machinery, has been reported as an adaptive response to maintain metabolic homeostasis when cancer cells encounter stress. It has been appreciated that autophagy acts as a double-edge sword to decide the fate of cancer cells upon stress factors, molecular subtypes, and microenvironmental conditions. Currently, the majority of evidence support that autophagy in cancer cells is a vital mechanism bringing on resistance to current and prospective treatments, yet whether autophagy affects the anticancer immune response remains unclear and controversial...
June 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28619711/igfbp7-deletion-promotes-hepatocellular-carcinoma
#8
Maaged Akiel, Chunqing Guo, Xia Li, Devaraja Rajasekaran, Rachel G Mendoza, Chadia L Robertson, Nidhi Jariwala, Fang Yuan, Mark A Subler, Jolene Windle, Dawn K Garcia, Zhao Lai, Hung-I Harry Chen, Yidong Chen, Shah Giashuddin, Paul B Fisher, Xiang-Yang Wang, Devanand Sarkar
Activation of IGF signaling is a major oncogenic event in diverse cancers, including hepatocellular carcinoma (HCC). In this setting, the insulin-like growth factor binding protein IGFBP7 inhibits IGF signaling by binding the IGF-1 receptor (IGF-1R), functioning as a candidate tumor suppressor. IGFBP7 abrogates tumors by inhibiting angiogenesis and inducing cancer-specific senescence and apoptosis. Here we report that Igfbp7-deficient mice exhibit constitutively active IGF signaling, presenting with pro-inflammatory and immunosuppressive microenvironments and spontaneous liver and lung tumors occurring with increased incidence in carcinogen-treated subjects...
June 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28614624/new-insights-into-the-role-of-emt-in-tumor-immune-escape
#9
REVIEW
Stéphane Terry, Pierre Savagner, Sandra Ortiz-Cuaran, Linda Mahjoubi, Pierre Saintigny, Jean-Paul Thiery, Salem Chouaib
Novel immunotherapy approaches have provided durable remission in a significant number of cancer patients with cancers previously considered rapidly lethal. Nonetheless, the high degree of non-responders, and in some cases the emergence of resistance in patients who do initially respond, represents a significant challenge in the field of cancer immunotherapy. These issues prompt much more extensive studies to better understand how cancer cells escape immune surveillance and resist immune attacks. Here, we review the current knowledge of how cellular heterogeneity and plasticity could be involved in shaping the tumor microenvironment and in controlling anti-tumor immunity...
June 14, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28582845/elevated-lactate-dehydrogenase-ldh-can-be-a-marker-of-immune-suppression-in-cancer-interplay-between-hematologic-and-solid-neoplastic-clones-and-their-microenvironments
#10
Jennifer Ding, Judith E Karp, Ashkan Emadi
Metabolism of neoplastic cells is shifted toward high glucose uptake and enhanced lactate production. Lactate dehydrogenase (LDH), which is comprised of two major subunits, LDH-A and LDH-B, reversibly catalyzes the conversion of pyruvate to lactate or lactate to pyruvate. LDH-A has a higher affinity for pyruvate and is a key enzyme in the glycolytic pathway. Elevated LDH is a negative prognostic biomarker not only because it is a key enzyme involved in cancer metabolism, but also because it allows neoplastic cells to suppress and evade the immune system by altering the tumor microenvironment...
May 19, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28581441/nk-cell-heparanase-controls-tumor-invasion-and-immune-surveillance
#11
Eva M Putz, Alyce J Mayfosh, Kevin Kos, Deborah S Barkauskas, Kyohei Nakamura, Liam Town, Katharine J Goodall, Dean Y Yee, Ivan Kh Poon, Nikola Baschuk, Fernando Souza-Fonseca-Guimaraes, Mark D Hulett, Mark J Smyth
NK cells are highly efficient at preventing cancer metastasis but are infrequently found in the core of primary tumors. Here, have we demonstrated that freshly isolated mouse and human NK cells express low levels of the endo-β-D-glucuronidase heparanase that increase upon NK cell activation. Heparanase deficiency did not affect development, differentiation, or tissue localization of NK cells under steady-state conditions. However, mice lacking heparanase specifically in NK cells (Hpsefl/fl NKp46-iCre mice) were highly tumor prone when challenged with the carcinogen methylcholanthrene (MCA)...
June 5, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28576921/novel-elements-of-immune-suppression-within-the-tumor-microenvironment
#12
REVIEW
Devikala Gurusamy, David Clever, Robert Eil, Nicholas P Restifo
Adaptive evolution has prompted immune cells to use a wide variety of inhibitory signals, many of which are usurped by tumor cells to evade immune surveillance. Although tumor immunologists often focus on genes and proteins as mediators of immune function, here we highlight two elements from the periodic table-oxygen and potassium-that suppress the immune system in previously unappreciated ways. While both are key to the maintenance of T-cell function and tissue homeostasis, they are exploited by tumors to suppress immuno-surveillance and promote metastatic spread...
June 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28556451/skin-cancers-in-organ-transplant-recipients
#13
Amit Mittal, Oscar R Colegio
Long-term utilization of immunosuppression in organ transplant recipients (OTRs) leads to decreased immune-mediated tumor surveillance and development of malignant tumors. A delicate balance needs to be maintained in the intensity of immunosuppression to keep the risk of malignancy low without jeopardizing life-saving graft function. OTRs are prone to developing skin cancers which exhibit unique epidemiologic, pathophysiologic and prognostic characteristics. In this review, we discuss the most commonly reported skin cancers in OTRs: squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Kaposi's sarcoma, Merkel cell carcinoma and malignant melanoma (MM)...
May 29, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28551443/impact-of-perioperative-infection-on-cancer-specific-survival-after-nephrectomy-for-renal-cell-carcinoma
#14
Jacob E Tallman, Shane M Pearce, Kristine Kuchta, Brian T Helfand, Scott E Eggener
INTRODUCTION: Several case reports have documented rare spontaneous cancer regression following systemic infections. Immune-related targeted therapies are now available for many cancers, including renal cell carcinoma (RCC). We hypothesized perioperative infection following nephrectomy for RCC may impact long-term cancer-specific survival (CSS). METHODS: We performed a retrospective cohort study using Surveillance, Epidemiology, and End Results (SEER)-Medicare claims data from 2004-2011...
May 24, 2017: Journal of Urology
https://www.readbyqxmd.com/read/28537924/genetic-defects-of-the-irf1-mediated-major-histocompatibility-complex-class-i-antigen-presentation-pathway-occur-prevalently-in-the-jak2-gene-in-non-small-cell-lung-cancer
#15
Tao Shen, Zhengming Chen, Zhizhuang Joe Zhao, Jie Wu
Recognition of major histocompatibility complex (MHC) class I antigens on tumor cells by cytotoxic T cells is involved in T cell-mediated tumor immune surveillance and immune checkpoint therapy. The interferon-γ (IFNγ)-IRF1 signaling pathway regulates MHC class I antigen presentation. To examine genetic defects of the IFNγ-IRF1 pathway in non-small cell lung cancer (NSCLC), we analyzed The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LuAd) and lung squamous cell carcinoma (LuSc) data. Loss-of-function (LOF) genetic alterations of the IFNγ-IRF1 pathway genes (IFNGR1, IFNGR2, JAK1, JAK2, STAT1, IRF1) were found in 64 (6...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28536458/epigenetic-priming-restores-the-hla-class-i-antigen-processing-machinery-expression-in-merkel-cell-carcinoma
#16
Cathrin Ritter, Kaiji Fan, Annette Paschen, Sine Reker Hardrup, Soldano Ferrone, Paul Nghiem, Selma Ugurel, David Schrama, Jürgen C Becker
Merkel cell carcinoma (MCC) is a rare and aggressive, yet highly immunogenic skin cancer. The latter is due to its viral or UV-associated carcinogenesis. For tumor progression MCC has to escape the host's immuno-surveillance, e.g. by loss of HLA class-I expression. Indeed, a reduced HLA class-I expression was observed in MCC tumor tissues and MCC cell lines. This reduced HLA class-I surface expression is caused by an impaired expression of key components of the antigen processing machinery (APM), including LMP2 and LMP7 as well as TAP1 and TAP2...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28533942/hla-a24-ligandome-analysis-of-colon-and-lung-cancer-cells-identifies-a-novel-cancer-testis-antigen-and-a-neoantigen-that-elicits-specific-and-strong-ctl-responses
#17
Vitaly Kochin, Takayuki Kanaseki, Serina Tokita, Sho Miyamoto, Yosuke Shionoya, Yasuhiro Kikuchi, Daichi Morooka, Yoshihiko Hirohashi, Tomohide Tsukahara, Kazue Watanabe, Shingo Toji, Yasuo Kokai, Noriyuki Sato, Toshihiko Torigoe
This study focused on HLA-A24 and comprehensively analyzed the ligandome of colon and lung cancer cells without the use of MHC-binding in silico prediction algorithms. Affinity purification using the antibody specific to HLA-A24 followed by LC-MS/MS sequencing was used to detect peptides, which harbored the known characteristics of HLA-A24 peptides in terms of length and anchor motifs. Ligandome analysis demonstrated the natural presentation of two different types of novel tumor-associated antigens. The ligandome contained a peptide derived from SUV39H2, a gene found to be expressed in a variety of cancers but not in normal tissues (except for the testis)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28527911/cancer-stem-cells-at-the-forefront-of-personalized-medicine-and-immunotherapy
#18
REVIEW
Micol E Fiori, Lidia Villanova, Ruggero De Maria
Cancer stem cells (CSCs) represent the main target of the current efforts to eradicate cancer, because of their ability to promote metastatic dissemination and survive cytotoxic therapies. Here, we highlight the potential of patient-derived CSCs as an in vitro and in vivo pre-clinical model and of liquid biopsy as a diagnostic, prognostic and predictive tool. We discuss recently developed therapeutic strategies aiming at specifically targeting the cancer stem cell population, particularly focusing on the latest advances in cancer immunotherapy...
May 18, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28526770/therapeutic-ige-antibodies-harnessing-a-macrophage-mediated-immune-surveillance-mechanism-against-cancer
#19
REVIEW
Sophia N Karagiannis, Debra H Josephs, Heather J Bax, James F Spicer
IgG monoclonal antibodies have made significant contributions to cancer therapy, but suffer from several limitations that restrict their effectiveness in unleashing host immune system components against tumors. The development of monoclonal antibodies of an alternative class, namely IgE, may offer enhanced immune surveillance and superior effector cell potency against cancer cells. In our recent article, we elaborate our proof-of-concept studies of a mouse/human chimeric IgE antibody (MOv18 IgE), which is specific for the cancer-associated antigen folate receptor alpha...
May 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/28523199/de-novo-pten-mutation-in-a-young-boy-with-cutaneous-vasculitis
#20
Angela Mauro, Ebun Omoyinmi, Neil James Sebire, Angela Barnicoat, Paul Brogan
Phosphatase and tensin homolog (PTEN) is the protein encoded by the PTEN gene (10q23.3). PTEN mutations are related to a variety of rare diseases referred to collectively as PTEN hamartoma tumor syndromes (PHTS), which include Cowden Syndrome, Bannayan-Riley-Ruvalcaba syndrome, Proteus Syndrome, and Proteus-like syndrome. These diseases are associated with an increased risk of malignancy and for this reason an accurate and early diagnosis is essential in order to institute cancer surveillance. PTEN is a regulator of growth and homeostasis in immune system cells, although there are limited data describing immune dysregulation caused by PTEN mutations...
2017: Case Reports in Pediatrics
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