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Cancer Immunology, Immunotherapy: CII

Nathan Karin, Hila Razon
Bone marrow (BM) cells of the hematopoietic system, also known as BM-derived leukocytes (BMD), are mobilized from the BM to the blood and then colonize tumor sites. These cells then become key players in either promoting or regulating the development and progression of tumors. Among the cells that suppress anti-tumor immunity are regulatory T cells (Tregs ), tumor-associated macrophages (TAMS) and myeloid-derived suppressor cells (MDSC). MDSC comprise CD11b+ Gr1+ Ly6Clow polymorphonuclear myeloid cells (PMN-MDSC), and CD11b+ Gr1+ Ly6Chigh monocytic myeloid cells (Mo-MDSC)...
September 19, 2018: Cancer Immunology, Immunotherapy: CII
Jeong-Hoon Lee, Joon Hyeok Lee, Young-Suk Lim, Jong Eun Yeon, Tae-Jin Song, Su Jong Yu, Geum-Youn Gwak, Kang Mo Kim, Yoon Jun Kim, Jae Won Lee, Jung-Hwan Yoon
Our earlier multicenter randomized controlled trial showed that adjuvant immunotherapy with cytokine-induced killer (CIK) cells resulted in longer recurrence-free survival (RFS) and overall survival (OS) as well in patients who received curative treatment for hepatocellular carcinoma (HCC). In the present study, we determined if the efficacy of CIK cell therapy continued after end of repeated CIK cell injections. We performed a follow-up study of our preceding trial. We included 226 patients: 114 patients in the immunotherapy group (injection of 6...
September 19, 2018: Cancer Immunology, Immunotherapy: CII
Benjamin L Solomon, Ignacio Garrido-Laguna
Treatment strategies for patients with advanced solid tumors have traditionally been based on three different paradigms: surgery, cytotoxics (chemotherapy or radiation therapy) and targeted therapies. Immunotherapy has emerged as a novel treatment paradigm in our armamentarium. Unfortunately, most patients still do not benefit from immunotherapy. These patients often have "cold tumors" characterized by a paucity of effector T cells in the tumor microenvironment, low mutational load, low neoantigen burden and often an immunosuppressive tumor microenvironment...
September 19, 2018: Cancer Immunology, Immunotherapy: CII
Guanxi Qiao, Mark J Bucsek, Nicolette M Winder, Minhui Chen, Thejaswini Giridharan, Scott H Olejniczak, Bonnie L Hylander, Elizabeth A Repasky
Primary and secondary lymphoid organs are heavily innervated by the autonomic nervous system. Norepinephrine, the primary neurotransmitter secreted by post-ganglionic sympathetic neurons, binds to and activates β-adrenergic receptors expressed on the surface of immune cells and regulates the functions of these cells. While it is known that both activated and memory CD8+ T-cells primarily express the β2-adrenergic receptor (β2-AR) and that signaling through this receptor can inhibit CD8+ T-cell effector function, the mechanism(s) underlying this suppression is not understood...
September 18, 2018: Cancer Immunology, Immunotherapy: CII
Henning Zelba, Jonas Bochem, Graham Pawelec, Claus Garbe, Kilian Wistuba-Hamprecht, Benjamin Weide
Increasing numbers of trials employing anti-PD-1 immunotherapy emphasize the requirement for predictive biomarkers of clinical response. Many studies examine the cell surface expression of PD-1 and other key regulators of T-cell activation and inhibition. Here, we compared common commercially available anti-PD-1 diagnostic antibodies and tested whether they can bind the PD-1 receptor in the presence of the therapeutic antagonists pembrolizumab and nivolumab. We observed that currently no antibodies are available that can reliably stain all PD-1 receptors on T-cells from patients treated with anti-PD-1 antibodies...
September 14, 2018: Cancer Immunology, Immunotherapy: CII
Jhanelle E Gray, Alberto Chiappori, Charlie C Williams, Tawee Tanvetyanon, Eric B Haura, Ben C Creelan, Jongphil Kim, Theresa A Boyle, Mary Pinder-Schenck, Farah Khalil, Soner Altiok, Rebecca Devane, David Noyes, Melanie Mediavilla-Varela, Renee Smilee, Emily L Hopewell, Linda Kelley, Scott J Antonia
The GM.CD40L vaccine, which recruits and activates dendritic cells, migrates to lymph nodes, activating T cells and leading to systemic tumor cell killing. When combined with the CCL21 chemokine, which recruits T cells and enhances T-cell responses, additive effects have been demonstrated in non-small cell lung cancer mouse models. Here, we compared GM.CD40L versus GM.CD40L plus CCL21 (GM.CD40L.CCL21) in lung adenocarcinoma patients with ≥ 1 line of treatment. In this phase I/II randomized trial (NCT01433172), patients received intradermal vaccines every 14 days (3 doses) and then monthly (3 doses)...
September 12, 2018: Cancer Immunology, Immunotherapy: CII
Alexander N R Weber, Yamel Cardona Gloria, Özcan Çınar, H Christian Reinhardt, Antonio Pezzutto, Olaf-Oliver Wolz
Oncogenic MYD88 mutations, most notably the Leu 265 Pro (L265P) mutation, were recently identified as potential driver mutations in various B-cell non-Hodgkin Lymphomas (NHLs). The L265P mutation is now thought to be common to virtually all NHLs and occurs in between 4 and 90% of cases, depending on the entity. Since it is tumor-specific, the mutation, and the pathways it regulates, might serve as advantageous therapeutic targets for both conventional chemotherapeutic intervention, as well as immunotherapeutic strategies...
September 11, 2018: Cancer Immunology, Immunotherapy: CII
Allison S Dobry, Cheryl K Zogg, F Stephen Hodi, Timothy R Smith, Patrick A Ott, J Bryan Iorgulescu
BACKGROUND: Immune checkpoint blockade (ICB) and BRAFV600 -targeted therapy have demonstrated substantial clinical efficacy for patients with stage 4 melanoma in clinical trials; however, their impact on survival and barriers to treatment in the "real-life" setting remains unknown. METHODS: Patients who presented with cutaneous melanoma during 2004-2015 using the National Cancer Database, which comprises > 70% of all newly diagnosed cancers in the U...
September 6, 2018: Cancer Immunology, Immunotherapy: CII
Pedro Berraondo, Maria Angela Aznar, Elisabeth Perez-Ruiz, Maria Esperanza Rodriguez-Ruiz, Eduardo Castañon, Jose Luis Perez-Gracia, Ignacio Melero
No abstract text is available yet for this article.
September 4, 2018: Cancer Immunology, Immunotherapy: CII
Sabine Schmid, Stefan Diem, Qiyu Li, Mirjam Krapf, Lukas Flatz, Sebastian Leschka, Lotus Desbiolles, Dirk Klingbiel, Wolfram Jochum, Martin Früh
BACKGROUND: Response to immune checkpoint inhibitors depends on tumor intrinsic properties and also on host factors in the tumour microenvironment including the presence of immune cells (IC). We hypothesized that nivolumab efficacy varies across different metastatic sites. METHODS: We retrospectively analyzed computed tomography scans of patients with metastatic non-small cell lung carcinoma (NSCLC) receiving nivolumab. RECIST 1.1 criteria were applied to assess the overall response rate (ORR) and organ-specific response rate (OSRR)...
August 31, 2018: Cancer Immunology, Immunotherapy: CII
Ya-Bin Jin, Wei Luo, Guo-Yi Zhang, Kai-Rong Lin, Jin-Huan Cui, Xiang-Ping Chen, Ying-Ming Pan, Xiao-Fan Mao, Jun Tang, Yue-Jian Wang
The T-cell immune responses in nasopharyngeal carcinoma patients have been extensively investigated recently for designing adoptive immunotherapy or immune checkpoint blockade therapy. However, the distribution characteristics of T cells associated with NPC pathogenesis are largely unknown. We performed deep sequencing for TCR repertoire profiling on matched tumor/adjacent normal tissue from 15 NPC patients and peripheral blood from 39 NPC patients, 39 patients with other nasopharyngeal diseases, and 33 healthy controls...
August 28, 2018: Cancer Immunology, Immunotherapy: CII
John Wahba, Marina Natoli, Lynsey M Whilding, Ana C Parente-Pereira, Youngrock Jung, Stefania Zona, Eric W-F Lam, J Richard Smith, John Maher, Sadaf Ghaem-Maghami
Epithelial ovarian cancer (EOC) is the most lethal of all gynecological malignancies in the UK. Recent evidence has shown that there is potential for immunotherapies to be successful in treating this cancer. We have previously shown the effective application of combinations of traditional chemotherapy and CAR (chimeric antigen receptor) T cell immunotherapy in in vitro and in vivo models of EOC. Platinum-based chemotherapy synergizes with ErbB-targeted CAR T cells (named T4), significantly reducing tumor burden in mice...
August 24, 2018: Cancer Immunology, Immunotherapy: CII
Matthew P Alexander, Steven N Fiering, Gary R Ostroff, Robert A Cramer, David W Mullins
β-Glucan is a naturally occurring glucose polysaccharide with immunostimulatory activity in both infection and malignancy. β-Glucan's antitumor effects have been attributed to the enhancement of complement receptor 3-dependent cellular cytotoxicity, as well as modulation of suppressive and stimulatory myeloid subsets, which in turn enhances antitumor T cell immunity. In the present study, we demonstrate antitumor efficacy of yeast-derived β-glucan particles (YGP) in a model of metastatic-like melanoma in the lung, through a mechanism that is independent of previously reported β-glucan-mediated antitumor pathways...
August 23, 2018: Cancer Immunology, Immunotherapy: CII
Chao Yang, He Cheng, Yiyin Zhang, Kun Fan, Guopei Luo, Zhiyao Fan, Qiuyi Huang, Yu Lu, Kaizhou Jin, Zhengshi Wang, Xianjun Yu, Chen Liu
INTRODUCTION: Natural killer cells (NK) are often believed to play a positive role in the antitumor immune response. However, this is not the case for patients with advanced pancreatic cancer. This study was performed to determine the unique subtype of "educated" NK cells and their prognostic value in patients with advanced pancreatic cancer. METHODS: We divided 378 eligible patients into a derivation cohort (September 2010 to December 2014, n = 239) and a validation cohort (January 2015 to April 2016, n = 139)...
August 22, 2018: Cancer Immunology, Immunotherapy: CII
Andreas Wieland, Alice O Kamphorst, N Volkan Adsay, Jonathan J Masor, Juan Sarmiento, Tahseen H Nasti, Sam Darko, Daniel C Douek, Yue Xue, Walter J Curran, David H Lawson, Rafi Ahmed
PD-1-targeted therapy has dramatically changed advanced cancer treatment. However, many questions remain, including specificity of T cells activated by PD-1 therapy and how peripheral blood analysis correlates to effects at tumor sites. In this study, we utilized TCR sequencing to dissect the composition of peripheral blood CD8 T cells activated upon therapy, comparing it with tumor-infiltrating lymphocytes. We report on a nonagenarian melanoma patient who showed a prominent increase in peripheral blood Ki-67 + CD8 T cells following brain stereotactic radiation and anti-PD-1 immunotherapy...
August 22, 2018: Cancer Immunology, Immunotherapy: CII
Kai-Rong Lin, Dan-Mei Pang, Ya-Bin Jin, Qian Hu, Ying-Ming Pan, Jin-Huan Cui, Xiang-Ping Chen, Yin-Xin Lin, Xiao-Fan Mao, Hai-Bo Duan, Wei Luo
PURPOSE: CD8+ T cells are primarily cytotoxic cells that provide immunological protection against malignant cells. Considerable evidence suggests that the T-cell repertoire is closely associated with the host immune response and the development of cancer. In this study, we explored the characteristics of the circulating CD8+ T-cell repertoire and their potential value in predicting the clinical response of breast cancer patients to chemotherapy. EXPERIMENTAL DESIGN: We applied a high-throughput TCR β-chain sequencing method to characterize the CD8+ T-cell repertoire of the peripheral blood from 26 breast cancer patients...
August 22, 2018: Cancer Immunology, Immunotherapy: CII
Yu Yao, Feifei Luo, Chao Tang, Dikang Chen, Zhiyong Qin, Wei Hua, Ming Xu, Ping Zhong, Shuangquan Yu, Di Chen, Xiaojie Ding, Yi Zhang, Xiujuan Zheng, Jiao Yang, Jiawen Qian, Yuting Deng, Dave S B Hoon, Jian Hu, Yiwei Chu, Liangfu Zhou
Dendritic cell (DC)-based vaccination is a promising approach for active-specific immunotherapy, but is currently of limited efficacy. The safety and effectiveness of a DC vaccine (DCV) loaded with glioblastoma stem cell-like (GSC) antigens was assessed in glioblastoma multiforme (GBM) patients. In this double-blind, placebo-controlled phase II clinical trial, 43 GBM patients were randomized after surgery at a 1:1 ratio to receive either DCV (n = 22) or normal saline placebo (n = 21). Overall survival (OS) and progression-free survival (PFS) were analysed...
August 22, 2018: Cancer Immunology, Immunotherapy: CII
Frank Neumann, Fabian Acker, Claudia Schormann, Michael Pfreundschuh, Joerg Thomas Bittenbring
Vitamin D3 (25-OH-D3) deficiency impairs rituximab-dependent cellular cytotoxicity and the outcome of patients with diffuse large B-cell and follicular lymphomas (DLBCL). Since the optimum 25-OH-D3 serum levels for NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) are unknown, we determined the 25-OH-D3 serum levels associated with maximum NK cell-mediated ADCC. CD20 antibody-loaded CD20+ B-cell lymphoma cell lines were cultured with NK cells and ADCC activity was determined by lactate dehydrogenase release assays...
August 21, 2018: Cancer Immunology, Immunotherapy: CII
S M Mansour Haeryfar, Todd D Schell
PD-1- and PD-L1-blocking monoclonal antibodies have shown significant promise in clinical settings and rekindled the hope for successful cancer immunotherapy. We recently demonstrated that interfering with PD-1/PD-L1 signaling selectively augments CD8+ T cell (TCD8 ) responses to subdominant determinants (SDDs) of a model tumor antigen. This was likely due to decreased lysis of SDD-specific TCD8 by neighboring immunodominant clones co-engaging the same antigen-presenting cells (APCs). We therefore proposed that PD-1-based checkpoint inhibitors widen the range of tumor determinants that can be effectively targeted by TCD8 ...
August 21, 2018: Cancer Immunology, Immunotherapy: CII
Julian Plaumann, Melanie Engelhardt, Mohamed H S Awwad, Hakim Echchannaoui, Eva Amman, Marc S Raab, Jens Hillengass, Niels Halama, Brigitte Neuber, Carsten Müller-Tidow, Hartmut Goldschmidt, Michael Hundemer
Tumor-mediated immunosuppression via regulatory T-cells is a key player among the various immune-escape mechanisms in multiple myeloma. We analyzed the generation, distribution, function and immunophenotype of CD8+ CD28- regulatory T-cells in patients with multiple myeloma. Functionality of CD8+ CD28- T-cells was assessed by immunological assays using ex vivo generated antigen-specific T-cells from patients with plasma cell dyscrasias and healthy donors. Detailed analysis of distribution, immunophenotype and cytotoxic potential of CD8+ CD28- T-cells was performed by flow cytometry and ELISA...
August 20, 2018: Cancer Immunology, Immunotherapy: CII
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