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NK cell immune checkpoint blockade

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https://www.readbyqxmd.com/read/30048638/overcoming-immune-suppression-with-epigenetic-modification-in-ovarian-cancer
#1
REVIEW
Tyler R McCaw, Troy D Randall, Rebecca C Arend
The impressive successes of immunotherapy have yet to be reliably translated to treatment of ovarian cancer, which may be a consequence of the unique barriers to T cell migration and tumor engagement in the peritoneal cavity and omentum. Epigenetic alterations contribute to establishment of these barriers and other mechanisms of immune subversion; therefore, epigenetic modifying agents represent an opportunity to mount effective antitumor immune responses by disrupting this finely tuned tumor epigenetic framework...
June 23, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30048003/the-yin-yang-of-the-interaction-between-myelomonocytic-cells-and-nk-cells
#2
REVIEW
Martina Molgora, Domenico Supino, Domenico Mavilio, Angela Santoni, Lorenzo Moretta, Alberto Mantovani, Cecilia Garlanda
NK cells are innate lymphoid cells, which play a key role in the immune response to cancer and pathogens and participate in the shaping of adaptive immunity. NK cells engage in a complex bidirectional interaction with myelomonocytic cells. In particular, macrophages, dendritic cells and neutrophils promote differentiation and effector function of NK cells and, on the other hand, myelomonocytic cells express triggers of checkpoint blockade (e.g. PD-L1) and other immunosuppressive molecules, which negatively regulate NK cell function...
July 24, 2018: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/30006382/natural-killer-cells-enhance-immune-checkpoint-blockade-efficacy
#3
(no author information available yet)
Natural killer (NK) cell interactions with stimulatory dendritic cells (SDC) enhance immunotherapy.
July 13, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29934472/immune-checkpoint-blockade-restores-hiv-specific-cd4-t-cell-help-for-nk-cells
#4
Filippos Porichis, Meghan G Hart, Alexandra Massa, Holly L Everett, Antigoni Morou, Jonathan Richard, Nathalie Brassard, Maxime Veillette, Muska Hassan, Ngoc Le Ly, Jean-Pierre Routy, Gordon J Freeman, Mathieu Dubé, Andrés Finzi, Daniel E Kaufmann
Immune exhaustion is an important feature of chronic infections, such as HIV, and a barrier to effective immunity against cancer. This dysfunction is in part controlled by inhibitory immune checkpoints. Blockade of the PD-1 or IL-10 pathways can reinvigorate HIV-specific CD4 T cell function in vitro, as measured by cytokine secretion and proliferative responses upon Ag stimulation. However, whether this restoration of HIV-specific CD4 T cells can improve help to other cell subsets impaired in HIV infection remains to be determined...
August 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29921599/experimental-lung-metastases-in-mice-are-more-effectively-inhibited-by-blockade-of-il23r-than-il23
#5
Juming Yan, Stacey Allen, Dipti Vijayan, Xian-Yang Li, Heidi Harjunpää, Kazuyoshi Takeda, Jing Liu, Daniel J Cua, Mark J Smyth, Michele W L Teng
Tumor-induced immunosuppression is mediated through various mechanisms including engagement of immune checkpoint receptors on effector cells, function of immunoregulatory cells such as regulatory T cells and myeloid-derived suppressor cells, and deployment of immunosuppressive cytokines such as TGFβ and IL10. IL23 is a cytokine that negatively affects antitumor immunity. In this study, we investigated whether IL23-deficient (IL23p19-/- ) and IL23R-deficient (IL23R-/- ) mice phenocopied each other, with respect to their tumor control...
August 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29915296/blockade-of-the-checkpoint-receptor-tigit-prevents-nk-cell-exhaustion-and-elicits-potent-anti-tumor-immunity
#6
Qing Zhang, Jiacheng Bi, Xiaodong Zheng, Yongyan Chen, Hua Wang, Wenyong Wu, Zhengguang Wang, Qiang Wu, Hui Peng, Haiming Wei, Rui Sun, Zhigang Tian
Checkpoint blockade enhances effector T cell function and has elicited long-term remission in a subset of patients with a broad spectrum of cancers. TIGIT is a checkpoint receptor thought to be involved in mediating T cell exhaustion in tumors; however, the relevance of TIGIT to the dysfunction of natural killer (NK) cells remains poorly understood. Here we found that TIGIT, but not the other checkpoint molecules CTLA-4 and PD-1, was associated with NK cell exhaustion in tumor-bearing mice and patients with colon cancer...
June 18, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29872559/rankl-blockade-improves-efficacy-of-pd1-pd-l1-blockade-or-dual-pd1-pd-l1-and-ctla4-blockade-in-mouse-models-of-cancer
#7
Elizabeth Ahern, Heidi Harjunpää, Jake S O'Donnell, Stacey Allen, William C Dougall, Michele W L Teng, Mark J Smyth
Receptor activator of NF-κB ligand (RANKL) and its receptor RANK, are members of the tumor necrosis factor and receptor superfamilies, respectively. Antibodies targeting RANKL have recently been evaluated in combination with anti-CTLA4 in case reports of human melanoma and mouse models of cancer. However, the efficacy of anti-RANKL in combination with antibodies targeting other immune checkpoint receptors such as PD1 has not been reported. In this study, we demonstrated that blockade of RANKL improves anti-metastatic activity of antibodies targeting PD1/PD-L1 and improves subcutaneous growth suppression in mouse models of melanoma, prostate and colon cancer...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29871698/hemophagocytic-lymphohistiocytosis-with-immunotherapy-brief-review-and-case-report
#8
Masood Sadaat, Sekwon Jang
BACKGROUND: Hemophagocytic Lymphohistiocytosis (HLH), a rare but potentially fatal syndrome of immune hyperactivation, may be an under-recognized immune-related adverse event (irAE). Unlike other irAEs, HLH triggered by immune checkpoint blockade is not well described; no particular diagnostic guidelines and treatment regimens exist. The HLH-2004 criteria remain as the common diagnostic guide. For the treatment of HLH, various combinations of chemotherapeutic, immunosuppressive and glucocorticoid agents are used...
June 5, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29861604/tumor-immunotherapy-new-aspects-of-natural-killer-cells
#9
Yangxi Li, Rui Sun
A group of impressive immunotherapies for cancer treatment, including immune checkpoint-blocking antibodies, gene therapy and immune cell adoptive cellular immunotherapy, have been established, providing new weapons to fight cancer. Natural killer (NK) cells are a component of the first line of defense against tumors and virus infections. Studies have shown dysfunctional NK cells in patients with cancer. Thus, restoring NK cell antitumor functionality could be a promising therapeutic strategy. NK cells that are activated and expanded ex vivo can supplement malfunctional NK cells in tumor patients...
April 2018: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
https://www.readbyqxmd.com/read/29731749/adaptive-nkg2c-cd57-natural-killer-cell-and-tim-3-expression-during-viral-infections
#10
Hassen Kared, Serena Martelli, Shu Wen Tan, Yannick Simoni, Meng Li Chong, Siew Hwei Yap, Evan W Newell, Sylvia L F Pender, Adeeba Kamarulzaman, Reena Rajasuriar, Anis Larbi
Repetitive stimulation by persistent pathogens such as human cytomegalovirus (HCMV) or human immunodeficiency virus (HIV) induces the differentiation of natural killer (NK) cells. This maturation pathway is characterized by the acquisition of phenotypic markers, CD2, CD57, and NKG2C, and effector functions-a process regulated by Tim-3 and orchestrated by a complex network of transcriptional factors, involving T-bet, Eomes, Zeb2, promyelocytic leukemia zinc finger protein, and Foxo3. Here, we show that persistent immune activation during chronic viral co-infections (HCMV, hepatitis C virus, and HIV) interferes with the functional phenotype of NK cells by modulating the Tim-3 pathway; a decrease in Tim-3 expression combined with the acquisition of inhibitory receptors skewed NK cells toward an exhausted and cytotoxic phenotype in an inflammatory environment during chronic HIV infection...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29721396/m7824-a-novel-bifunctional-anti-pd-l1-tgf%C3%AE-trap-fusion-protein-promotes-anti-tumor-efficacy-as-monotherapy-and-in-combination-with-vaccine
#11
Karin M Knudson, Kristin C Hicks, Xiaoling Luo, Jin-Qiu Chen, Jeffrey Schlom, Sofia R Gameiro
Tumors evade host immune surveillance through multiple mechanisms, including the generation of a tumor microenvironment that suppresses immune effector function. Secretion of TGFβ and upregulation of immune checkpoint programmed cell death ligand-1 (PD-L1) are two main contributors to immune evasion and tumor progression. Here, we examined the efficacy of a first-in-class bifunctional checkpoint inhibitor, the fusion protein M7824, comprising the extracellular domain of human TGFβRII (TGFβ Trap) linked to the C-terminus of human anti-PD-L1 heavy chain (αPD-L1)...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29721390/cd96-targeted-antibodies-need-not-block-cd96-cd155-interactions-to-promote-nk-cell-anti-metastatic-activity
#12
Amelia Roman Aguilera, Viviana P Lutzky, Deepak Mittal, Xian-Yang Li, Kimberley Stannard, Kazuyoshi Takeda, Günter Bernhardt, Michele W L Teng, William C Dougall, Mark J Smyth
CD96 is a transmembrane glycoprotein Ig superfamily receptor, expressed on various T cell subsets and NK cells, that interacts with nectin and nectin-like proteins, including CD155/polio virus receptor (PVR). Here, we have compared three rat anti-mouse CD96 mAbs, including two that block CD96-CD155 (3.3 and 6A6) and one that does not block CD96-CD155 (8B10). Using flow cytometry, we demonstrated that both mAbs 3.3 and 6A6 bind to the first Ig domain of mouse CD96 and compete with CD155 binding, while mAb 8B10 binds to the second Ig domain and does not block CD155...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29515971/the-expression-and-prognostic-impact-of-immune-cytolytic-activity-related-markers-in-human-malignancies-a-comprehensive-meta-analysis
#13
Constantinos Roufas, Dimitrios Chasiotis, Anestis Makris, Christodoulos Efstathiades, Christos Dimopoulos, Apostolos Zaravinos
Background: Recently, immune-checkpoint blockade has shown striking clinical results in different cancer patients. However, a significant inter-individual and inter-tumor variability exists among different cancers. The expression of the toxins granzyme A (GZMA) and perforin 1 (PRF1), secreted by effector cytotoxic T cells and natural killer (NK) cells, were recently used as a denominator of the intratumoral immune cytolytic activity (CYT). These levels are significantly elevated upon CD8+ T-cell activation as well as during a productive clinical response against immune-checkpoint blockade therapies...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29510697/distinct-predictive-biomarker-candidates-for-response-to-anti-ctla-4-and-anti-pd-1-immunotherapy-in-melanoma-patients
#14
Priyanka B Subrahmanyam, Zhiwan Dong, Daniel Gusenleitner, Anita Giobbie-Hurder, Mariano Severgnini, Jun Zhou, Michael Manos, Lauren M Eastman, Holden T Maecker, F Stephen Hodi
BACKGROUND: While immune checkpoint blockade has greatly improved clinical outcomes in diseases such as melanoma, there remains a need for predictive biomarkers to determine who will likely benefit most from which therapy. To date, most biomarkers of response have been identified in the tumors themselves. Biomarkers that could be assessed from peripheral blood would be even more desirable, because of ease of access and reproducibility of sampling. METHODS: We used mass cytometry (CyTOF) to comprehensively profile peripheral blood of melanoma patients, in order to find predictive biomarkers of response to anti-CTLA-4 or anti-PD-1 therapy...
March 6, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29456538/an-uncoupling-of-canonical-phenotypic-markers-and-functional-potency-of-ex-vivo-expanded-natural-killer-cells
#15
Nicole A P Lieberman, Kole DeGolier, Kristen Haberthur, Harrison Chinn, Kara W Moyes, Myriam N Bouchlaka, Kirsti L Walker, Christian M Capitini, Courtney A Crane
Recent advances in cellular therapies for patients with cancer, including checkpoint blockade and ex vivo -expanded, tumor-specific T cells, have demonstrated that targeting the immune system is a powerful approach to the elimination of tumor cells. Clinical efforts have also demonstrated limitations, however, including the potential for tumor cell antigenic drift and neoantigen formation, which promote tumor escape and recurrence, as well as rapid onset of T cell exhaustion in vivo . These findings suggest that antigen unrestricted cells, such as natural killer (NK) cells, may be beneficial for use as an alternative to or in combination with T cell based approaches...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29431745/dkk2-imparts-tumor-immunity-evasion-through-%C3%AE-catenin-independent-suppression-of-cytotoxic-immune-cell-activation
#16
Qian Xiao, Jibo Wu, Wei-Jia Wang, Shiyang Chen, Yingxia Zheng, Xiaoqing Yu, Katrina Meeth, Mahnaz Sahraei, Alfred L M Bothwell, Lieping Chen, Marcus Bosenberg, Jianfeng Chen, Veronika Sexl, Le Sun, Lin Li, Wenwen Tang, Dianqing Wu
Immunotherapy offers new options for cancer treatment, but efficacy varies across cancer types. Colorectal cancers (CRCs) are largely refractory to immune-checkpoint blockade, which suggests the presence of yet uncharacterized immune-suppressive mechanisms. Here we report that the loss of adenomatosis polyposis coli (APC) in intestinal tumor cells or of the tumor suppressor PTEN in melanoma cells upregulates the expression of Dickkopf-related protein 2 (DKK2), which, together with its receptor LRP5, provides an unconventional mechanism for tumor immune evasion...
March 2018: Nature Medicine
https://www.readbyqxmd.com/read/29396703/immunologic-milieu-of-mature-t-cell-and-nk-cell-lymphomas-implications-for-therapy
#17
REVIEW
Eric Tse, Yok-Lam Kwong
PURPOSE OF THE REVIEW: T-cells and natural killer (NK) cells share the same ontogeny, and lymphomas derived from them are clinically diverse, occurring in nodal and extranodal sites. In addition to inherent properties of these lymphomas, their microenvironment also impacts on pathogenesis and response to therapy. An understanding of the milieu of T-cell and NK cell lymphomas has important implications on treatment. RECENT FINDINGS: Components of the microenvironment include tumour-associated macrophages (TAM), non-neoplastic T-cells and B-cells, eosinophils, dendritic cells, endothelial cells and blood vessels...
February 2018: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/29386395/anti-pd-1-anti-ctla-4-efficacy-in-melanoma-brain-metastases-depends-on-extracranial-disease-and-augmentation-of-cd8-t-cell-trafficking
#18
David Taggart, Tereza Andreou, Karen J Scott, Jennifer Williams, Nora Rippaus, Rebecca J Brownlie, Elizabeth J Ilett, Robert J Salmond, Alan Melcher, Mihaela Lorger
Inhibition of immune checkpoints programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) on T cells results in durable antitumor activity in melanoma patients. Despite high frequency of melanoma brain metastases (BrM) and associated poor prognosis, the activity and mechanisms of immune checkpoint inhibitors (ICI) in metastatic tumors that develop within the "immune specialized" brain microenvironment, remain elusive. We established a melanoma tumor transplantation model with intracranial plus extracranial (subcutaneous) tumor, mimicking the clinically observed coexistence of metastases inside and outside the brain...
February 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29349763/immune-checkpoint-blockade-for-breast-cancer
#19
REVIEW
April Swoboda, Rita Nanda
An effective antitumor immune response requires interaction between cells of the adaptive and innate immune system. Three key elements are required: generation of activated tumor-directed T cells, infiltration of activated T cells into the tumor microenvironment, and killing of tumor cells by activated T cells. Tumor immune evasion can occur as a result of the disruption of each of these three key T cell activities, resulting in three distinct cancer-immune phenotypes. The immune inflamed phenotype, characterized by the presence of a robust tumor immune infiltrate, suggests impaired activated T cell killing of tumor cells related to the presence of inhibitory factors...
2018: Cancer Treatment and Research
https://www.readbyqxmd.com/read/29339375/tusc2-immunogene-therapy-synergizes-with-anti-pd-1-through-enhanced-proliferation-and-infiltration-of-natural-killer-cells-in-syngeneic-kras-mutant-mouse-lung-cancer-models
#20
Ismail M Meraz, Mourad Majidi, Xiaobo Cao, Heather Lin, Lerong Li, Jing Wang, Veera Baladandayuthapani, David Rice, Boris Sepesi, Lin Ji, Jack A Roth
Expression of the multikinase inhibitor encoded by the tumor suppressor gene TUSC2 (also known as FUS1 ) is lost or decreased in non-small cell lung carcinoma (NSCLC). TUSC2 delivered systemically by nanovesicles has mediated tumor regression in clinical trials. Because of the role of TUSC2 in regulating immune cells, we assessed TUSC2 efficacy on antitumor immune responses alone and in combination with anti-PD-1 in two Kras -mutant syngeneic mouse lung cancer models. TUSC2 alone significantly reduced tumor growth and prolonged survival compared with anti-PD-1...
February 2018: Cancer Immunology Research
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