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Cancer Immunology, Immunotherapy: CII

Viktor Umansky, Gosse J Adema, Jaroslaw Baran, Sven Brandau, Jo A Van Ginderachter, Xiaoying Hu, Jadwiga Jablonska, Slavko Mojsilovic, Helen A Papadaki, Yago Pico de Coaña, Kim C M Santegoets, Juan F Santibanez, Karine Serre, Yu Si, Isabela Sieminska, Maria Velegraki, Zvi G Fridlender
Mounting evidence has accumulated on the critical role of the different myeloid cells in the regulation of the cancerous process, and in particular in the modulation of the immune reaction to cancer. Myeloid cells are a major component of host cells infiltrating tumors, interacting with each other, with tumor cells and other stromal cells, and demonstrating a prominent plasticity. We describe here various myeloid regulatory cells (MRCs) in mice and human as well as their relevant therapeutic targets. We first address the role of the monocytes and macrophages that can contribute to angiogenesis, immunosuppression and metastatic dissemination...
July 12, 2018: Cancer Immunology, Immunotherapy: CII
Tonke K Raaijmakers, Marleen Ansems
Dendritic cells (DCs) are widely used in DC-based immunotherapies because of their capacity to steer immune responses. So far treatment success is limited and more functional knowledge on how DCs initiate and stably drive specific responses is needed. Many intrinsic and extrinsic factors contribute to how DCs skew the immune response towards immunity or tolerance. The origin and type of DC, its maturation status, but also factors they encounter in the in vitro or in vivo microenvironment they reside in during differentiation and maturation affect this balance...
July 11, 2018: Cancer Immunology, Immunotherapy: CII
Nobuko Matsuura, Genju Koh, Chihiro Konishi, Satoshi Minamino, Yoshinori Takahara, Hiromasa Harada, Ken Kodama, Masanori Emoto
Programmed cell death-1 (PD-1) and programmed cell death-ligand-1 (PD-L1) inhibitors have been highlighted in the field of cancer treatment. The interaction between PD-1 and PD-L1 is thought to play an important role in the regulation of the self-immune tolerance mechanism, so blocking these molecules may cause serious immune-related adverse events (IrAE), including fulminant insulin-dependent (type 1) diabetes. Here, we describe a patient with fulminant type 1 diabetes induced by nivolumab, an anti-PD-1 antibody...
July 11, 2018: Cancer Immunology, Immunotherapy: CII
Hemant K Mishra, Nabendu Pore, Emil F Michelotti, Bruce Walcheck
Several clinically successful tumor-targeting mAbs induce NK cell effector functions. Human NK cells exclusively recognize tumor-bound IgG by the FcR CD16A (FcγRIIIA). Unlike other NK cell activating receptors, the cell surface density of CD16A can be rapidly downregulated in a cis manner by the metalloproteinase ADAM17 following NK cell stimulation in various manners. CD16A downregulation takes place in cancer patients and this may affect the efficacy of tumor-targeting mAbs. We examined the effects of MEDI3622, a human mAb and potent ADAM17 inhibitor, on NK cell activation by antibody-bound tumor cells...
July 5, 2018: Cancer Immunology, Immunotherapy: CII
Ruben Lacroix, Elisa A Rozeman, Marina Kreutz, Kathrin Renner, Christian U Blank
Checkpoint inhibitors, such as cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) and programmed cell death-1 (PD-1) monoclonal antibodies have changed profoundly the treatment of melanoma, renal cell carcinoma, non-small cell lung cancer, Hodgkin lymphoma, and bladder cancer. Currently, they are tested in various tumor entities as monotherapy or in combination with chemotherapies or targeted therapies. However, only a subgroup of patients benefit from checkpoint blockade (combinations). This raises the question, which all mechanisms inhibit T cell function in the tumor environment, restricting the efficacy of these immunotherapeutic approaches...
July 5, 2018: Cancer Immunology, Immunotherapy: CII
Lourdes Barrera, Edgar Montes-Servín, Juan-Manuel Hernandez-Martinez, Mario Orozco-Morales, Elizabeth Montes-Servín, David Michel-Tello, Renato Augusto Morales-Flores, Diana Flores-Estrada, Oscar Arrieta
Polymorphonuclear-MDSC (PMN-MDSC) have emerged as an independent prognostic factor for survival in NSCLC. Similarly, cytokine profiles have been used to identify subgroups of NSCLC patients with different clinical outcomes. This prospective study investigated whether the percentage of circulating PMN-MDSC, in conjunction with the levels of plasma cytokines, was more informative of disease progression than the analysis of either factor alone. We analyzed the phenotypic and functional profile of peripheral blood T-cell subsets (CD3+ , CD3+ CD4+ and CD3+ CD8+ ), neutrophils (CD66b+ ) and polymorphonuclear-MDSC (PMN-MDSC; CD66b+ CD11b+ CD15+ CD14-) as well as the concentration of 14 plasma cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 p70, IL-17A, IL-27, IL-29, IL-31, and IL-33, TNF-α, IFN-γ) in 90 treatment-naïve NSCLC patients and 25 healthy donors (HD)...
July 4, 2018: Cancer Immunology, Immunotherapy: CII
Roberto De Luca, Dario Neri
We have recently described a novel therapeutic antibody product (IL2-F8-TNFmut ), featuring the simultaneous fusion of murine IL2 and of a TNF mutant with scFv(F8), an antibody specific to the alternatively-spliced extra domain A of fibronectin (EDA). Here, we report on the in vivo characterization of the anti-cancer activity of IL2-F8-TNFmut in four immunocompetent murine models of cancer, CT26, WEHI-164, F9 teratocarcinoma and Lewis lung carcinoma (LLC), using the product alone or in combination with a monoclonal antibody specific to murine PD-L1...
July 4, 2018: Cancer Immunology, Immunotherapy: CII
Wataru Obara, Isao Hara, Yoichiro Kato, Renpei Kato, Keiji Inoue, Fuminori Sato, Hiromitsu Mimata, Yusuke Nakamura, Tomoaki Fujioka
PURPOSE: A phase I study using two peptide vaccines derived from M phase phosphoprotein 1 (MPHOSPH1) and DEP domain containing 1 (DEPDC1) demonstrated promising results for the treatment of advanced bladder cancer. Therefore, we further tested the ability of these peptides to prevent recurrence after transurethral resection of the bladder tumor in patients with non-muscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS: 127 patients were enrolled in a multicenter, non-randomized phase II clinical trial...
July 3, 2018: Cancer Immunology, Immunotherapy: CII
Kaushal Parikh, Arun Kumar, Jibran Ahmed, Asad Anwar, Carmelo Puccio, Hoo Chun, Michael Fanucchi, Seah H Lim
We carried out a retrospective cohort study on patients with metastatic non-small cell lung cancer (mNSCLC) to identify the peripheral blood count parameters associated with response to immune checkpoint inhibitors (ICIs). There were 17 males and 15 females. Their median age was 64.5 years (range 20-84). History of smoking was present in 25/32 (78%) patients. Twelve patients received pembrolizumab, 19 patients nivolumab, and one patient nivolumab followed by pembrolizumab. Responses were observed in 19/32 (59%) patients, all partial responses...
July 2, 2018: Cancer Immunology, Immunotherapy: CII
Yuting Deng, Jiao Yang, Feifei Luo, Jing Qian, Ronghua Liu, Dan Zhang, Hongxiu Yu, Yiwei Chu
Immune cell activation occurs concurrently with metabolic reprogramming. As important components of the tumor microenvironment, monocytic myeloid-derived suppressor cells (M-MDSCs) are featured by their potent immunosuppressive abilities on anti-tumor effector cells. However, little is known about the contribution of metabolic adaptations to their suppressive roles. In this study, we found that tumor-infiltrating M-MDSCs had the same phenotype with splenic M-MDSCs. Compared with splenic M-MDSCs, tumor-infiltrating M-MDSCs exhibited stronger suppressive activities which was accompanied by higher glycolysis...
July 2, 2018: Cancer Immunology, Immunotherapy: CII
Zachary J Brown, Su Jong Yu, Bernd Heinrich, Chi Ma, Qiong Fu, Milan Sandhu, David Agdashian, Qianfei Zhang, Firouzeh Korangy, Tim F Greten
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. Immune checkpoint blockade with anti-CTLA-4 and anti-PD-1 antibodies has shown promising results in the treatment of patients with advanced HCC. The anti-PD-1 antibody, nivolumab, is now approved for patients who have had progressive disease on the current standard of care. However, a subset of patients with advanced HCC treated with immune checkpoint inhibitors failed to respond to therapy. Here, we provide evidence of adaptive resistance to immune checkpoint inhibitors through upregulation of indoleamine 2,3-dioxygenase (IDO) in HCC...
June 29, 2018: Cancer Immunology, Immunotherapy: CII
Luana Calabrò, Aldo Morra, Robin Cornelissen, Joachim Aerts, Michele Maio
Treatment of malignant pleural mesothelioma (MPM) represents a highly unmet medical need. Here, we discuss the results and therapeutic potential of first- and second-generation immunomodulatory antibodies targeting distinct immune checkpoints for the treatment of MPM, as well as their prospective therapeutic role in combination strategies. We also discuss the role of appropriate radiological criteria of response for MPM and the potential need of ad hoc criteria of disease evaluation in MPM patients undergoing treatment with immunotherapeutic agents...
June 26, 2018: Cancer Immunology, Immunotherapy: CII
Georgia Karpathiou, Celine Chauleur, Sirine Hathroubi, Cyril Habougit, Michel Peoc'h
BACKGROUND: Mammary and extra-mammary Paget disease is a rare form of intra-epithelial glandular neoplasm which is characteristically recurrent and necessitates multiple excisions that have an important impact on morbidity. Local immuno-modulating treatments have been applied with promising results, but the local immune markers of Paget disease have not been studied. AIM OF THE STUDY: To investigate the local immune micro-environment of Paget disease. MATERIALS AND METHODS: Sixty-four specimens from 41 patients, including cases with multiple recurrences and underlying primary neoplasm, have been studied for their expression of CD3, PD-L1 and CTLA-4...
June 25, 2018: Cancer Immunology, Immunotherapy: CII
Sarah C Krzastek, Ekaterine Goliadze, Shaoqing Zhou, Albert Petrossian, Fatma Youniss, Gobalakrishnan Sundaresan, Li Wang, Jamal Zweit, Georgi Guruli
Prostate cancer is one of the leading causes of cancer deaths, with no curative treatments once it spreads. Alternative therapies, including immunotherapy, have shown limited efficacy. Dendritic cells (DC) have been widely used in the treatment of various malignancies. DC capture antigens and move to the lymphoid organs where they prime naive T cells. Interaction between DC and T cells are most active in lymph nodes and suppression of DC trafficking to lymph nodes impairs the immune response. In this work, we aimed to study trafficking of DC in vivo via various routes of delivery, to optimize the effectiveness of DC-based therapy...
June 25, 2018: Cancer Immunology, Immunotherapy: CII
Valeria I Segatori, Héctor A Cuello, Cynthia A Gulino, Marina Albertó, Cecilia Venier, Marcelo D Guthmann, Ignacio A Demarco, Daniel F Alonso, Mariano R Gabri
Antitumor strategies based on positive modulation of the immune system currently represent therapeutic options with prominent acceptance for cancer patients' treatment due to its selectivity and higher tolerance compared to chemotherapy. Racotumomab is an anti-idiotype (anti-Id) monoclonal antibody (mAb) directed to NeuGc-containing gangliosides such as NeuGcGM3, a widely reported tumor-specific neoantigen in many human cancers. Racotumomab has been approved in Latin American countries as an active immunotherapy for advanced non-small cell lung cancer (NSCLC) treatment...
June 23, 2018: Cancer Immunology, Immunotherapy: CII
Robert D Leone, Im-Meng Sun, Min-Hee Oh, Im-Hong Sun, Jiayu Wen, Judson Englert, Jonathan D Powell
Adenosine signaling via the A2a receptor (A2aR) is emerging as an important checkpoint of immune responses. The presence of adenosine in the inflammatory milieu or generated by the CD39/CD73 axis on tissues or T regulatory cells serves to regulate immune responses. By nature of the specialized metabolism of cancer cells, adenosine levels are increased in the tumor microenvironment and contribute to tumor immune evasion. To this end, small molecule inhibitors of the A2aR are being pursued clinically to enhance immunotherapy...
June 19, 2018: Cancer Immunology, Immunotherapy: CII
Roberto Ruiu, Valeria Rolih, Elisabetta Bolli, Giuseppina Barutello, Federica Riccardo, Elena Quaglino, Irene Fiore Merighi, Federica Pericle, Gaetano Donofrio, Federica Cavallo, Laura Conti
Tumor relapse and metastatic spreading act as major hindrances to achieve complete cure of breast cancer. Evidence suggests that cancer stem cells (CSC) would function as a reservoir for the local and distant recurrence of the disease, due to their resistance to radio- and chemotherapy and their ability to regenerate the tumor. Therefore, the identification of appropriate molecular targets expressed by CSC may be critical in the development of more effective therapies. Our studies focused on the identification of mammary CSC antigens and on the development of CSC-targeting vaccines...
June 15, 2018: Cancer Immunology, Immunotherapy: CII
Carlo Putzu, Diego Luigi Cortinovis, Francesca Colonese, Stefania Canova, Ciriaco Carru, Angelo Zinellu, Panagiotis Paliogiannis
Lung cancer is the most common malignancy worldwide. Despite significant advances in diagnosis and treatment, mortality rates remain extremely high, close to incidence rates. Several targeted therapies have been recently introduced for the treatment of non-small cell lung cancer (NSCLC), the most common type of lung cancer. Nivolumab, a monoclonal antibody that targets programmed death-1 (PD-1), was the first immune checkpoint inhibitor approved for the treatment of patients with advanced/metastatic NSCLC not responding to platinum-based chemotherapy...
June 9, 2018: Cancer Immunology, Immunotherapy: CII
Christos Sachpekidis, Hoda Anwar, Julia K Winkler, Annette Kopp-Schneider, Lionel Larribere, Uwe Haberkorn, Jessica C Hassel, Antonia Dimitrakopoulou-Strauss
BACKGROUND: Immunotherapy has raised the issue of appropriate treatment response evaluation, due to the unique mechanism of action of the immunotherapeutic agents. Aim of this analysis is to evaluate the potential role of quantitative analysis of 2-deoxy-2-(18 F)fluoro-D-glucose (18 F-FDG) positron emission tomography/computed tomography (PET/CT) data in monitoring of patients with metastatic melanoma undergoing ipilimumab therapy. METHODS: 25 patients with unresectable metastatic melanoma underwent dynamic PET/CT (dPET/CT) of the thorax and upper abdomen as well as static, whole body PET/CT with 18 F-FDG before the start of ipilimumab treatment (baseline PET/CT), after two cycles of treatment (interim PET/CT) and at the end of treatment after four cycles (late PET/CT)...
June 5, 2018: Cancer Immunology, Immunotherapy: CII
Kasper Mølgaard, Seandean L Harwood, Marta Compte, Nekane Merino, Jaume Bonet, Ana Alvarez-Cienfuegos, Kasper Mikkelsen, Natalia Nuñez-Prado, Ana Alvarez-Mendez, Laura Sanz, Francisco J Blanco, Luis Alvarez-Vallina
The recruitment of T-cells by bispecific antibodies secreted from adoptively transferred, gene-modified autologous cells has shown satisfactory results in preclinical cancer models. Even so, the approach's translation into the clinic will require incremental improvements to its efficacy and reduction of its toxicity. Here, we characterized a tandem T-cell recruiting bispecific antibody intended to benefit gene-based immunotherapy approaches, which we call the light T-cell engager (LiTE), consisting of an EGFR-specific single-domain VHH antibody fused to a CD3-specific scFv...
June 4, 2018: Cancer Immunology, Immunotherapy: CII
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