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Tumor immunotherapy

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https://www.readbyqxmd.com/read/29473504/immunotherapy-in-non-small-cell-lung-cancer-biological-principles-and-future-opportunities
#1
M Ilie, J Benzaquen, V Hofman, S Lassalle, N Yazbeck, S Leroy, S Heeke, C Bence, B Mograbi, N Glaichenhaus, C H Marquette, P Hofman
Immunotherapy aims to amplify the anticancer immune response through reactivation of the lymphocytic response raised against several tumor neo-antigens. To obtain an effective immune response, this therapeutic approach requires that a number of immunological checkpoints be passed, such as the activation of excitatory costimulatory signals or the avoidance of coinhibitory molecules. Among the immune checkpoints, the interaction of the membrane-bound ligand PD-1 and its receptor PD-L1 has received much attention because of remarkable efficacy in numerous clinical trials for various cancer types, including non-small cell lung cancer (NSCLC)...
February 21, 2018: Current Molecular Medicine
https://www.readbyqxmd.com/read/29473472/application-of-cancer-testis-antigens-in-immunotherapy-of-hepatocellular-carcinoma
#2
Mahnaz Seifi-Alan, Roshanak Shamsi, Soudeh Ghafouri-Fard
Hepatocellular carcinoma (HCC) is a worldwide common malignancy with poor prognosis. Several studies have aimed at identification of appropriate biomarkers for early detection of this cancer. Cancer-testis antigens (CTAs) as a novel group of tumor-associated antigens have been demonstrated to be expressed in HCC samples as well as peripheral blood samples from these patients but not in the corresponding adjacent noncancerous samples. Such pattern of expression has provided them an opportunity to be used as immunotherapeutic targets...
April 2018: Immunotherapy
https://www.readbyqxmd.com/read/29473471/malignant-mesothelioma-clinical-trial-combines-immunotherapy-drugs
#3
Monica S Chatwal, Tawee Tanvetyanon
Immunotherapy by checkpoint inhibitor is effective for a number of solid tumors including malignant mesothelioma. Studies utilizing single-agent PD-1 or PD-L1 inhibitor for mesothelioma have reported tumor response rates in approximately 10-20% of patients treated. Given the success of combining these agents with CTLA-4 inhibitor in melanoma, there is a strong rationale to study it in mesothelioma. Recently results from clinical trials investigating this approach have been released. Though limited by small sample size, the studies conclusively demonstrated feasibility and suggested a modestly higher tumor response rate than one would expect from treatment with single-agent PD-1 or PD-L1 inhibitor...
April 2018: Immunotherapy
https://www.readbyqxmd.com/read/29473266/anti-human-sirp%C3%AE-antibody-is-a-new-tool-for-cancer-immunotherapy
#4
Yoji Murata, Daisuke Tanaka, Daisuke Hazama, Tadahiko Yanagita, Yasuyuki Saito, Takenori Kotani, Per-Arne Oldenborg, Takashi Matozaki
Interaction of signal regulatory protein α (SIRPα) expressed on the surface of macrophages with its ligand CD47 expressed on target cells negatively regulates phagocytosis of the latter cells by the former. We recently showed that blocking Abs to mouse SIRPα enhanced both the Ab-dependent cellular phagocytosis (ADCP) activity of mouse macrophages for Burkitt's lymphoma Raji cells opsonized with an Ab to CD20 (rituximab) in vitro as well as the inhibitory effect of rituximab on the growth of tumors formed by Raji cells in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice...
February 23, 2018: Cancer Science
https://www.readbyqxmd.com/read/29472932/-in-vitro-generated-tc17-cells-present-a-memory-phenotype-and-serve-as-a-reservoir-of-tc1-cells-in-vivo
#5
Felipe Flores-Santibáñez, Bárbara Cuadra, Dominique Fernández, Mariana V Rosemblatt, Sarah Núñez, Pablo Cruz, Felipe Gálvez-Cancino, J César Cárdenas, Alvaro Lladser, Mario Rosemblatt, María Rosa Bono, Daniela Sauma
Memory CD8+ T cells are ideal candidates for cancer immunotherapy because they can mediate long-term protection against tumors. However, the therapeutic potential of different in vitro -generated CD8+ T cell effector subsets to persist and become memory cells has not been fully characterized. Type 1 CD8+ T (Tc1) cells produce interferon-γ and are endowed with high cytotoxic capacity, whereas IL-17-producing CD8+ T (Tc17) cells are less cytotoxic but display enhanced self-renewal capacity. We sought to evaluate the functional properties of in vitro -generated Tc17 cells and elucidate their potential to become long lasting memory cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29472691/a-reappraisal-of-ctla-4-checkpoint-blockade-in-cancer-immunotherapy
#6
Xuexiang Du, Fei Tang, Mingyue Liu, Juanjuan Su, Yan Zhang, Wei Wu, Martin Devenport, Christopher A Lazarski, Peng Zhang, Xu Wang, Peiying Ye, Changyu Wang, Eugene Hwang, Tinghui Zhu, Ting Xu, Pan Zheng, Yang Liu
It is assumed that anti-CTLA-4 antibodies cause tumor rejection by blocking negative signaling from B7-CTLA-4 interactions. Surprisingly, at concentrations considerably higher than plasma levels achieved by clinically effective dosing, the anti-CTLA-4 antibody Ipilimumab blocks neither B7 trans-endocytosis by CTLA-4 nor CTLA-4 binding to immobilized or cell-associated B7. Consequently, Ipilimumab does not increase B7 on dendritic cells (DCs) from either CTLA4 gene humanized (Ctla4h/h ) or human CD34+ stem cell-reconstituted NSG™ mice...
February 22, 2018: Cell Research
https://www.readbyqxmd.com/read/29472052/thymic-tumors-revisiting-autoimmunity-to-give-a-chance-to-immunotherapy
#7
EDITORIAL
Nicolas Girard
No abstract text is available yet for this article.
March 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29471776/t-cell-immunotherapies-and-the-role-of-nonclinical-assessment-the-balance-between-efficacy-and-pathology
#8
Michaela E Sharpe
Gene-engineered T-cell therapies have the potential to revolutionize the treatment of cancer. These therapies have shown exceptional clinical efficacy specifically in the field of B-cell malignancies and the first products (Kymriah™ and Yescarta™) have recently been approved in the United States for specific indications. The power of these treatments is also linked with a distinct set of toxicities both predicted and unpredicted, including off-tumor activity, cytokine release syndromes, and neurotoxicity, occasionally with fatal consequences...
February 2018: Toxicologic Pathology
https://www.readbyqxmd.com/read/29471676/results-and-challenges-of-immune-checkpoint-inhibitors-in-colorectal-cancer
#9
Sheik Emambux, Gaelle Tachon, Audelaure Junca, David Tougeron
Introduction Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide and clinical outcome has improved substantially during the last two decades with targeted therapies. The immune system has a major role in cancers, especially the CD8+ T cells specific to tumor antigens. However, tumors can escape immune response by different mechanisms including upregulation of inhibitory immune checkpoint receptors, such as well-known Programmed cell Death protein-1 (PD-1)/Programmed cell Death Ligand 1 (PD-L1) interaction, leading CD8+ T cells to a state of anergy...
February 22, 2018: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29470831/expression-and-function-of-immune-ligand-receptor-pairs-in-nk-cells-and-cancer-stem-cells-therapeutic-implications
#10
REVIEW
Ioannis A Voutsadakis
BACKGROUND: The interplay between the immune system and cancer cells has come to the forefront of cancer therapeutics, with novel immune blockade inhibitors being approved for the treatment of an increasing list of cancers. However, the majority of cancer patients still display or develop resistance to these promising drugs. It is possible that cancer stem cells (CSCs) are contributing to this therapeutic resistance. Although CSCs usually represent a small percentage of the total number of cancer cells, they are endowed with the ability of self-renewal and to produce differentiated progeny...
February 22, 2018: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/29470785/the-abscopal-effect-in-the-era-of-cancer-immunotherapy-a-spontaneous-synergism-boosting-anti-tumor-immunity
#11
Zuzana Hlavata, Cinzia Solinas, Pushpamali De Silva, Michele Porcu, Luca Saba, Karen Willard-Gallo, Mario Scartozzi
Radiotherapy is one of the main treatment strategies used in cancer. Aside from the local control of the disease, which is mediated by a direct cytotoxic effect on tumor cells, radiotherapy has also been shown to exert immune-mediated local and systemic effects. Radiotherapy can elicit anti-tumor responses in distant sites from the radiation field; this phenomenon is known as the abscopal effect and has been described in patients previously treated with immune checkpoint blockade (ICB). Considering that the efficacy of immunotherapy has been demonstrated only in a subset of patients-who often benefit with lasting responses-efforts are ongoing to potentiate its activity with the development of new combination strategies...
February 22, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29470597/mucosa-associated-invariant-t-cells-in-malignancies-a-faithful-friend-or-formidable-foe
#12
REVIEW
S M Mansour Haeryfar, Christopher R Shaler, Patrick T Rudak
Mucosa-associated invariant T (MAIT) cells are a subset of innate-like T lymphocytes known for their ability to respond to MHC-related protein 1 (MR1)-restricted stimuli and select cytokine signals. They are abundant in humans and especially enriched in mucosal layers, common sites of neoplastic transformation. MAIT cells have been found within primary and metastatic tumors. However, whether they promote malignancy or contribute to anticancer immunity is unclear. On the one hand, MAIT cells produce IL-17A in certain locations and under certain circumstances, which could in turn facilitate neoangiogenesis, intratumoral accumulation of immunosuppressive cell populations, and cancer progression...
February 22, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29468660/spatiotemporal-homogeneity-and-distinctness-of-the-t-cell-receptor-%C3%AE-chain-repertoires-in-epstein-barr-virus-associated-primary-and-metastatic-nasopharyngeal-carcinomas
#13
Yih-Lin Chung, Mei-Ling Wu
Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated lymphoepithelioma. The aim of the present study was to characterize the homogeneity and distinctness of the T-cell repertoires within and between primary and metastatic NPCs. We used ultra-deep sequencing of the hypervariably rearranged antigen-binding CDR3 regions of T-cell receptor beta (TCRbeta ) to comprehensively profile the T-cell repertoires in NPC patients receiving definitive chemoradiotherapy with long-term follow-up. We observed not only various spatially heterogeneous patient-specific TCRbeta clone compositions that changed with time but also several commonly enriched TCRbeta subclones that were constantly shared between primary NPCs in the head and neck regions, locally recurrent tumors after treatment, and later-developed distant metastatic tumors in the liver, lung and bone...
February 22, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29468445/tumor-microenvironment-after-biodegradable-bcnu-wafer-implantation-special-consideration-of-immune-system
#14
Ichiyo Shibahara, Mitsuto Hanihara, Takashi Watanabe, Mitsuru Dan, Sumito Sato, Hiroki Kuroda, Akinori Inamura, Madoka Inukai, Atsuko Hara, Yoshie Yasui, Toshihiro Kumabe
Biomaterials to treat cancers hold therapeutic potential; however, their translation to bedside treatment requires further study. The carmustine (1,3-bis (2-chloroethyl)-1-nitrosourea; BCNU) wafer, a biodegradable polymer, currently is the only drug that is able to be placed at the surgical site to treat malignant tumors. However, how this wafer affects the surrounding tumor microenvironment is not well understood to date. We retrospectively reviewed all patients with glioblastoma treated with and without BCNU wafers who underwent repeat resection at tumor recurrence...
February 21, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29467871/abnormal-expression-of-circulating-and-tumor-infiltrating-carcinoembryonic-antigen-related-cell-adhesion-molecule-1-in-patients-with-glioma
#15
Jinhu Li, Xiaodong Liu, Yijun Duan, Hongqin Wang, Wen Su, Yazhou Wang, Guotao Zhuang, Yimin Fan
Glioma, the most prevalent primary tumor of the central nervous system, is known to evade immune surveillance and escape immune attacks by inducing immunosuppression. The homophilic interactions of the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) serve a critical function in immunoregulation. In the present study, the expression levels of CEACAM1 in peripheral blood mononuclear cells and tumor-infiltrating lymphocytes (TILs) from patients with gliomas were assessed. Furthermore, associations between CEACAM1 expression and multiple clinicopathological characteristics in patients with gliomas were analyzed...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29467463/bifunctional-immune-checkpoint-targeted-antibody-ligand-traps-that-simultaneously-disable-tgf%C3%AE-enhance-the-efficacy-of-cancer-immunotherapy
#16
Rajani Ravi, Kimberly A Noonan, Vui Pham, Rishi Bedi, Alex Zhavoronkov, Ivan V Ozerov, Eugene Makarev, Artem V Artemov, Piotr T Wysocki, Ranee Mehra, Sridhar Nimmagadda, Luigi Marchionni, David Sidransky, Ivan M Borrello, Evgeny Izumchenko, Atul Bedi
A majority of cancers fail to respond to immunotherapy with antibodies targeting immune checkpoints, such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) or programmed death-1 (PD-1)/PD-1 ligand (PD-L1). Cancers frequently express transforming growth factor-β (TGFβ), which drives immune dysfunction in the tumor microenvironment by inducing regulatory T cells (Tregs) and inhibiting CD8+ and TH 1 cells. To address this therapeutic challenge, we invent bifunctional antibody-ligand traps (Y-traps) comprising an antibody targeting CTLA-4 or PD-L1 fused to a TGFβ receptor II ectodomain sequence that simultaneously disables autocrine/paracrine TGFβ in the target cell microenvironment (a-CTLA4-TGFβRIIecd and a-PDL1-TGFβRIIecd)...
February 21, 2018: Nature Communications
https://www.readbyqxmd.com/read/29467128/macrophages-and-cd8-t-cells-mediate-the-anti-tumor-efficacy-of-combined-cd40-ligation-and-imatinib-therapy-in-gastrointestinal-stromal-tumors
#17
Jennifer Q Zhang, Shan Zeng, Gerardo A Vitiello, Adrian M Seifert, Benjamin D Medina, Michael J Beckman, Jennifer Loo, Juan Santamaria-Barria, Joanna H Maltbaek, Nesteene J Param, John A Moral, Julia N Zhao, Vinod Balachandran, Ferdinand Rossi, Cristina R Antonescu, Ronald P DeMatteo
Tyrosine kinase inhibition of gastrointestinal stromal tumors (GIST) is effective but typically culminates in resistance and is rarely curative. Immunotherapy has potential application to GIST, as we previously showed that T-cell checkpoint blockade increases the antitumor effects of imatinib. Here, we showed that ligation of CD40 using an agonistic antibody (anti-CD40) activated tumor-associated macrophages (TAMs) in vivo in a knock-in mouse model of GIST harboring a germline mutation in Kit exon 11. Activated TAMs had greater TNF production and NFkappaB signaling and directly inhibited tumor cells in vitro...
February 21, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29467127/quantitative-analysis-of-immune-infiltrates-in-primary-melanoma
#18
Robyn D Gartrell, Douglas K Marks, Thomas D Hart, Gen Li, Danielle R Davari, Alan Wu, Zoe Blake, Yan Lu, Kayleigh N Askin, Anthea Monod, Camden L Esancy, Edward C Stack, Dan Tong Jia, Paul M Armenta, Yichun Fu, Daisuke Izaki, Bret Taback, Raul Rabadan, Howard L Kaufman, Charles G Drake, Basil A Horst, Yvonne M Saenger
Novel methods to analyze the tumor microenvironment (TME) are urgently needed to stratify melanoma patients for adjuvant immunotherapy. Tumor infiltrating lymphocyte (TIL) analysis, by conventional pathologic methods, is predictive but is insufficiently precise for clinical application. Quantitative multiplex immunofluorescence (qmIF), allows for evaluation of the TME using multiparameter phenotyping, tissue segmentation, and quantitative spatial analysis (qSA). Given that CD3+CD8+ cytotoxic lymphocytes (CTLs) promote antitumor immunity, whereas CD68+ macrophages impair immunity, we hypothesized that quantification and spatial analysis of macrophages and CTLs would correlate with clinical outcome...
February 21, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29466856/enhanced-cellular-ablation-by-attenuating-hypoxia-status-and-reprogramming-tumor-associated-macrophages-via-nir-light-responsive-upconversion-nanocrystals
#19
Bengang Xing, Xiangzhao Ai, Ming Hu, Zhimin Wang, Linna Lyu, Wenmin Zhang, Jun Lin, Juan Li, Huang-Hao Yang
Near-infrared (NIR) light-mediated photodynamic therapy (PDT) especially based on lanthanide-doped upconversion nanocrystals (UCNs), have been extensively investigated as a promising strategy for effective cellular ablation owing to their unique optical properties to convert NIR light excitation into multiple short-wavelength emissions. Despite the deep tissue penetration of NIR light in living systems, the therapeutic efficiency is greatly restricted by insufficient oxygen supply in hypoxic tumor microenvironment...
February 21, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29466753/human-t-cell-development-localization-and-function-throughout-life
#20
REVIEW
Brahma V Kumar, Thomas J Connors, Donna L Farber
Throughout life, T cells coordinate multiple aspects of adaptive immunity, including responses to pathogens, allergens, and tumors. In mouse models, the role of T cells is studied in the context of a specific type of pathogen, antigen, or disease condition over a limited time frame, whereas in humans, T cells control multiple insults simultaneously throughout the body and maintain immune homeostasis over decades. In this review, we discuss how human T cells develop and provide essential immune protection at different life stages and highlight tissue localization and subset delineation as key determinants of the T cell functional role in immune responses...
February 20, 2018: Immunity
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