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Memory t cell cancer

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https://www.readbyqxmd.com/read/28228279/loss-of-pten-is-associated-with-resistance-to-anti-pd-1-checkpoint-blockade-therapy-in-metastatic-uterine-leiomyosarcoma
#1
Suzanne George, Diana Miao, George D Demetri, Dennis Adeegbe, Scott J Rodig, Sachet Shukla, Mikel Lipschitz, Ali Amin-Mansour, Chandrajit P Raut, Scott L Carter, Peter Hammerman, Gordon J Freeman, Catherine J Wu, Patrick A Ott, Kwok-Kin Wong, Eliezer M Van Allen
Response to immune checkpoint blockade in mesenchymal tumors is poorly characterized, but immunogenomic dissection of these cancers could inform immunotherapy mediators. We identified a treatment-naive patient who has metastatic uterine leiomyosarcoma and has experienced complete tumor remission for >2 years on anti-PD-1 (pembrolizumab) monotherapy. We analyzed the primary tumor, the sole treatment-resistant metastasis, and germline tissue to explore mechanisms of immunotherapy sensitivity and resistance...
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28205361/immunotherapy-against-metastatic-bladder-cancer-by-combined-administration-of-granulocyte-macrophage-colony-stimulating-factor-and-interleukin-2-surface-modified-mb49-bladder-cancer-stem-cells-vaccine
#2
Chun-Yan Wang, Rui Hua, Li Liu, Xiaomin Zhan, Simei Chen, Song Quan, Qing-Jun Chu, Yong-Tong Zhu
In previous studies, it has been shown that the granulocyte macrophage-colony stimulating factor (GM-CSF) or interleukin-2 (IL-2) surface modified MB49 bladder cancer stem cells (MCSCs) vaccine could induce a specific antitumor immunity and against bladder cancer in mice model respectively. However, whether combined administration of GM-CSF and IL-2 could produce specific immune responses to cancer stem cells (CSCs) was uncertain. MCSCs were established and characterized. GM-CSF and IL-2 MCSCs vaccines were prepared and bioactivity was evaluated...
February 16, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28197388/inhibition-of-tumor-growth-and-metastasis-by-emmprin-multiple-antigenic-peptide-map-vaccination-is-mediated-by-immune-modulation
#3
Elina Simanovich, Vera Brod, Maya M Rahat, Ella Drazdov, Miriam Walter, Jivan Shakya, Michal A Rahat
Previously, we have identified a new epitope in EMMPRIN, a multifunctional protein that mediates tumor cell-macrophage interactions and induces both MMP-9 and VEGF. Here, we synthesized this epitope as an octa-branched multiple antigenic peptide (MAP) to vaccinate mice implanted with subcutaneous syngeneic colon (CT26), prostate (TRAMP-C2) or renal (RENCA) cell line carcinomas. Vaccination inhibited, and sometimes regressed, tumor growth in a dose-dependent manner, reaching 94%, 71% and 72% inhibition, respectively, at a 50 μg dose (p < 0...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28197386/deficiency-of-the-immunostimulatory-cytokine-il-21-promotes-intestinal-neoplasia-via-dysregulation-of-the-th1-th17-axis
#4
Mia Shapiro, Bisweswar Nandi, Gabriel Gonzalez, Rao H Prabhala, Hiroshi Mashimo, Qin Huang, Natasha Y Frank, Nikhil C Munshi, Jason S Gold
IL-21 has reported activity in promoting both Th1 and Th17 immune responses. Its role in sporadic human colorectal cancer is unknown. We aimed to delineate the role of IL-21 in a model of sporadic intestinal carcinogenesis. We found that in APC(MIN/+) mice, ablation of IL-21 increased intestinal tumorigenesis. Expression of pro-inflammatory Th17-associated genes, including RORγt and IL-17A, was increased in the intestine in the absence of IL-21, while expression of antitumor Th1-associated genes Tbet, IFNγ, granzyme B, and perforin was decreased...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28197381/immunological-mechanisms-of-intravesical-chitosan-interleukin-12-immunotherapy-against-murine-bladder-cancer
#5
Sean G Smith, John L Baltz, Bhanu Prasanth Koppolu, Sruthi Ravindranathan, Khue Nguyen, David A Zaharoff
There is a critical unmet clinical need for bladder cancer immunotherapies capable of inducing durable antitumor immunity. We have shown that four intravesical treatments with a simple co-formulation of interleukin-12 and the biopolymer chitosan not only destroy orthotopic bladder tumors, but also promote a potent long-lasting systemic immune response as evidenced through tumor-specific in vitro killing assays, complete protection from rechallenge, and abscopal antitumor responses at distant non-treated tumors...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28196735/gtl001-and-bivalent-cyaa-based-therapeutic-vaccine-strategies-against-human-papillomavirus-and-other-tumor-associated-antigens-induce-effector-and-memory-t-cell-responses-that-inhibit-tumor-growth
#6
Michaël Esquerré, Marie Momot, Anne Goubier, Christophe Gonindard, Stéphane Leung-Theung-Long, Yolande Misseri, Marie-Christine Bissery
GTL001 is a bivalent therapeutic vaccine containing human papillomavirus (HPV) 16 and HPV18 E7 proteins inserted in the Bordetella pertussis adenylate cyclase (CyaA) vector intended to prevent cervical cancer in HPV-infected women with normal cervical cytology or mild abnormalities. To be effective, therapeutic cervical cancer vaccines should induce both a T cell-mediated effector response against HPV-infected cells and a robust CD8(+) T-cell memory response to prevent potential later infection. We examined the ability of GTL001 and related bivalent CyaA-based vaccines to induce, in parallel, effector and memory CD8(+) T-cell responses to both vaccine antigens...
February 10, 2017: Vaccine
https://www.readbyqxmd.com/read/28163164/anti-pd-1-pd-l1-therapy-for-infectious-diseases-learning-from-the-cancer-paradigm
#7
REVIEW
Martin Rao, Davide Valentini, Ernest Dodoo, Alimuddin Zumla, Markus Maeurer
OBJECTIVES: Immune checkpoint pathways regulate optimal host immune responses against transformed cells, induce immunological memory, and limit tissue pathology. Conversely, aberrant immune checkpoint activity signifies a poor prognosis in cancer and infectious diseases. Host-directed therapy (HDT) via immune checkpoint blockade has revolutionized cancer treatment with therapeutic implications for chronic infections, thus laying the foundation for this review. METHODS: Online literature searches were performed via PubMed, PubMed Central, and Google using the keywords "immune checkpoint inhibition"; "host-directed therapy"; "T cell exhaustion"; "cancer immunotherapy"; "anti-PD-1 therapy"; "anti-PD-L1 therapy"; "chronic infections"; "antigen-specific cells"; "tuberculosis"; "malaria"; "viral infections"; "human immunodeficiency virus"; "hepatitis B virus"; "hepatitis C virus"; "cytomegalovirus" and "Epstein-Barr virus"...
February 2, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28161000/-focus-on-the-immunoscore-and-its-potential-clinical-implications
#8
Carine El Sissy, Florence Marliot, Nacilla Haicheur, Amos Kirilovsky, Dragos Scripcariu, Christine Lagorce-Pagès, Jérôme Galon, Franck Pagès
The role of the immune response at the tumor site is now recognized as crucial in the clinical course of patients with cancer. The importance of the immune cell type, their functional orientation, their density and location within the tumor's regions (tumor/invasion margin) has recently been shown and were grouped together under the term "immune contexture". A strong infiltration by cytotoxic and memory T cells in a Th1-polarized tumor microenvironment appears to have a major prognosis impact. A test called Immunoscore taking into account these various parameters has been suggested to measure in a simple, reproducible and robust manner the intra- and peritumoral immune response...
February 2017: Annales de Pathologie
https://www.readbyqxmd.com/read/28152213/melatonin-signaling-in-t-cells-functions-and-applications
#9
REVIEW
Wenkai Ren, Gang Liu, Shuai Chen, Jie Yin, Jing Wang, Bie Tan, Guoyao Wu, Fuller W Bazer, Yuanyi Peng, Tiejun Li, Russel J Reiter, Yulong Yin
Melatonin affects a variety of physiological processes including circadian rhythms, cellular redox status and immune function. Importantly, melatonin significantly influences T cell-mediated immune responses, which are crucial to protect mammals against cancers and infections, but are associated with pathogenesis of many autoimmune diseases. This review focuses on our current understanding of the significance of melatonin in T cell biology and the beneficial effects of melatonin in T cell response-based diseases...
February 2, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28143493/the-yin-yan-of-ccl2-a-minor-role-in-neutrophil-anti-tumor-activity-in-vitro-but-a-major-role-on-the-outgrowth-of-metastatic-breast-cancer-lesions-in-the-lung-in-vivo
#10
Nicole Lavender, Jinming Yang, Sheau-Chiann Chen, Jiqing Sai, C Andrew Johnson, Philip Owens, Gregory D Ayers, Ann Richmond
BACKGROUND: The role of the chemokine CCL2 in breast cancer is controversial. While CCL2 recruits and activates pro-tumor macrophages, it is also reported to enhance neutrophil-mediated anti-tumor activity. Moreover, loss of CCL2 in early development enhances breast cancer progression. METHODS: To clarify these conflicting findings, we examined the ability of CCL2 to alter naïve and tumor entrained neutrophil production of ROS, release of granzyme-B, and killing of tumor cells in multiple mouse models of breast cancer...
January 31, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28138559/transient-stimulation-expands-superior-antitumor-t-cells-for-adoptive-therapy
#11
Yuki Kagoya, Munehide Nakatsugawa, Toshiki Ochi, Yuchen Cen, Tingxi Guo, Mark Anczurowski, Kayoko Saso, Marcus O Butler, Naoto Hirano
Adoptive cell therapy is a potentially curative therapeutic approach for patients with cancer. In this treatment modality, antitumor T cells are exponentially expanded in vitro prior to infusion. Importantly, the results of recent clinical trials suggest that the quality of expanded T cells critically affects their therapeutic efficacy. Although anti-CD3 mAb-based stimulation is widely used to expand T cells in vitro, a protocol to generate T cell grafts for optimal adoptive therapy has yet to be established...
January 26, 2017: JCI Insight
https://www.readbyqxmd.com/read/28129128/aptamer-targeted-attenuation-of-il-2-signaling-in-cd8-t-cells-enhances-antitumor-immunity
#12
Anugraha Rajagopalan, Alexey Berezhnoy, Brett Schrand, Yvonne Puplampu-Dove, Eli Gilboa
Immune responses elicited against cancer using existing therapies such as vaccines or immune stimulatory antibodies are often not curative. One way to potentiate antitumor immunity is to enhance the long-term persistence of anti-tumor CD8(+) T cells. Studies have shown that the persistence of activated CD8(+) T cells is negatively impacted by the strength of interleukin 2 (IL-2) signaling. Here, we used small interfering RNAs (siRNAs) against CD25 (IL-2Rα) to attenuate IL-2 signaling in CD8(+) T cells. The siRNAs were targeted to 4-1BB-expressing CD8(+) T cells by conjugation to a 4-1BB-binding oligonucleotide aptamer...
January 4, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28129117/immunosuppressive-myeloid-cells-blockade-in-the-glioma-microenvironment-enhances-the-efficacy-of-immune-stimulatory-gene-therapy
#13
Neha Kamran, Padma Kadiyala, Meghna Saxena, Marianela Candolfi, Youping Li, Mariela A Moreno-Ayala, Nicholas Raja, Diana Shah, Pedro R Lowenstein, Maria G Castro
Survival of glioma (GBM) patients treated with the current standard of care remains dismal. Immunotherapeutic approaches that harness the cytotoxic and memory potential of the host immune system have shown great benefit in other cancers. GBMs have developed multiple strategies, including the accumulation of myeloid-derived suppressor cells (MDSCs) to induce immunosuppression. It is therefore imperative to develop multipronged approaches when aiming to generate a robust anti-tumor immune response. Herein, we tested whether combining MDSC depletion or checkpoint blockade would augment the efficacy of immune-stimulatory herpes simplex type-I thymidine kinase (TK) plus Fms-like tyrosine kinase ligand (Flt3L)-mediated immune stimulatory gene therapy...
January 4, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28128200/the-immunoreceptor-nkg2d-promotes-tumour-growth-in-a-model-of-hepatocellular-carcinoma
#14
Sam Sheppard, Joana Guedes, Anna Mroz, Anastasia-Maria Zavitsanou, Hiromi Kudo, Stephen M Rothery, Panagiotis Angelopoulos, Robert Goldin, Nadia Guerra
Inflammation is recognized as one of the drivers of cancer. Yet, the individual immune components that possess pro- and anti-tumorigenic functions in individual cancers remain largely unknown. NKG2D is a potent activating immunoreceptor that has emerged as an important player in inflammatory disorders besides its well-established function as tumour suppressor. Here, we provide genetic evidence of an unexpected tumour-promoting effect of NKG2D in a model of inflammation-driven liver cancer. Compared to NKG2D-deficient mice, NKG2D-sufficient mice display accelerated tumour growth associated with, an increased recruitment of memory CD8(+)T cells to the liver and exacerbated pro-inflammatory milieu...
January 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28114190/cd8-foxp3-and-cd45ro-lymphocytic-infiltrates-in-type-i-and-type-ii-endometrial-cancers-in-african-american-and-european-american-females
#15
Tariq Rashid, Jennifer L Young-Pierce, Elizabeth Garrett-Mayer, Whitney Graybill, Shelby Neal, Laura S Spruill
African American (AA) females with endometrial carcinoma have a significantly worse prognosis with regard to disease-free survival and overall survival than their European American (EA) counterparts and this finding is true across all stages and grades. The presence of tumor-infiltrating lymphocytes (TILs) has been demonstrated to be of prognostic significance in a variety of malignancies, including endometrial cancers. This study aims to determine whether clinically significant differences in levels of CD8+ cytotoxic T lymphocytes, FoxP3+ regulatory T lymphocytes, and CD45RO+ memory T lymphocytes exist between races and to document the clinical impact of TILs...
January 20, 2017: International Journal of Gynecological Pathology
https://www.readbyqxmd.com/read/28108544/the-interplay-between-neutrophils-and-cd8-t-cells-improves-survival-in-human-colorectal-cancer
#16
Valeria Governa, Emanuele Trella, Valentina Mele, Luigi Tornillo, Francesca Amicarella, Eleonora Cremonesi, Maunele Giuseppe Muraro, Hui Xu, Raoul Droeser, Silvio Raffael Däster, Martin Bolli, Raffaele Rosso, Daniel Oertli, Serenella Eppenberger-Castori, Luigi Terracciano, Giandomenica Iezzi, Giulio C Spagnoli
PURPOSE: Tumor infiltration by different T lymphocyte subsets is known to be associated with favorable prognosis in colorectal cancer (CRC). Still debated is the role of innate immune system. We investigated clinical relevance, phenotypes and functional features of CRC infiltrating CD66b+ neutrophils and their crosstalk with CD8+ T cells. EXPERIMENTAL DESIGN: CD66b+ and CD8+ cell infiltration was analyzed by immunohistochemistry on a tissue microarray including >650 evaluable CRC samples...
January 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28101811/the-distribution-and-function-of-human-memory-t-cell-subsets-in-lung-cancer
#17
Si Yuan Sheng, Yong Gu, Chuan Gang Lu, Jian Yong Zou, Hai Hong, RongFu Wang
The distribution and function of T lymphocytes in human lung cancer remain limited. In this study, we investigated the properties of human T cell subsets in the blood of non-small cell lung cancer (NSCLC) patients. We found a relatively normal level of CD4+ subsets in the blood of NSCLC patients, but CD8+ effector T cells increased and CD8+ effector memory cells declined compared to the healthy donors. To further analyze their properties, we stimulated the peripheral blood mononuclear cells (PBMCs) of NSCLC patients by mitogens to examine cytokine production...
January 19, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28099920/prognostic-implications-of-intratumoral-cd103-tumor-infiltrating-lymphocytes-in-pulmonary-squamous-cell-carcinoma
#18
Jaemoon Koh, Sehui Kim, Moon-Young Kim, Heounjeong Go, Yoon Kyung Jeon, Doo Hyun Chung
CD103 is the αE subunit of αEβ7 integrin that is expressed in tissue-resident memory T cells, where it promotes cytotoxic T cell responses against tumors. However, little is known about its expression or clinicopathological implications in non-small cell lung cancer (NSCLC). This study investigated the prognostic implications of CD103+ tumor-infiltrating lymphocytes (TILs) in NSCLC. We established two cohorts: patients with resected NSCLC (n = 132) and patients with pulmonary squamous cell carcinoma (pSCC), a subset of NSCLC (n = 378), to estimate the prognostic significance of CD103+ TILs...
January 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28099502/clinical-and-immune-effects-of-lenalidomide-in-combination-with-gemcitabine-in-patients-with-advanced-pancreatic-cancer
#19
Gustav J Ullenhag, Fariba Mozaffari, Mats Broberg, Håkan Mellstedt, Maria Liljefors
PURPOSE: To assess the immunomodulatory and clinical effects of lenalidomide with standard treatment of gemcitabine in patients with advanced pancreatic cancer. PATIENTS AND METHODS: Patients with advanced pancreatic cancer were treated in first line with lenalidomide orally for 21 days of a 28 days cycle and the standard regimen for gemcitabine. In Part I, which we previously have reported, the dose of lenalidomide was defined (n = 12). In Part II, every other consecutive patient was treated with either lenalidomide (Group A, n = 11) or gemcitabine (Group B, n = 10) during cycle 1...
2017: PloS One
https://www.readbyqxmd.com/read/28096382/mitochondrial-activation-chemicals-synergize-with-surface-receptor-pd-1-blockade-for-t-cell-dependent-antitumor-activity
#20
Kenji Chamoto, Partha S Chowdhury, Alok Kumar, Kazuhiro Sonomura, Fumihiko Matsuda, Sidonia Fagarasan, Tasuku Honjo
Although immunotherapy by PD-1 blockade has dramatically improved the survival rate of cancer patients, further improvement in efficacy is required to reduce the fraction of less sensitive patients. In mouse models of PD-1 blockade therapy, we found that tumor-reactive cytotoxic T lymphocytes (CTLs) in draining lymph nodes (DLNs) carry increased mitochondrial mass and more reactive oxygen species (ROS). We show that ROS generation by ROS precursors or indirectly by mitochondrial uncouplers synergized the tumoricidal activity of PD-1 blockade by expansion of effector/memory CTLs in DLNs and within the tumor...
January 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
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