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Killer T cells cancer

Hu Luo, Liang Gong, Bingjing Zhu, Ying Huang, Chunlan Tang, Shicang Yu, Zhi Yang, Xiangdong Zhou
OBJECTIVE: Few clinical studies have confirmed the role of cytokine-induced killer cells (CIKs) in the maintenance therapy of advanced lung cancer patients. We investigate effectiveness and tolerability of CIKs as a maintenance therapy in the treatment of advanced lung cancer patients. METHODS: 70 patients with advanced lung cancer (stage IIIB to IV) admitted to the First Affiliated Hospital of Third Military Medical University in Chongqing from Nov. 2011 to Jan...
October 17, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Jing Ni, Oliver Hölsken, Matthias Miller, Quirin Hammer, Merlin Luetke-Eversloh, Chiara Romagnani, Adelheid Cerwenka
Natural killer (NK) cell infusions can induce remissions in subsets of patients with different types of cancer. The optimal strategies for NK cell activation prior to infusion are still under debate. There is recent evidence that NK cells can acquire long-term functional competence by preactivation with the cytokines IL-12/15/18. The mechanisms supporting the maintenance of long-term NK cell antitumor activity are incompletely under-stood. Here, we show that NK cells preactivated in vitro with IL-12/15/18, but not with IL-15 alone, maintained high antitumor activity even 1 mo after transfer into lymphopenic RAG-2(-/-)γc(-/-) mice...
2016: Oncoimmunology
Sreya Bagchi, Sha Li, Chyung-Ru Wang
Adoptive immunotherapy for cancer treatment is an emerging field of study. Till now, several tumor-derived, peptide-specific T cell responses have been harnessed for treating cancers. However, the contribution of lipid-specific T cells in tumor immunity has been understudied. CD1 molecules, which present self- and foreign lipid antigens to T cells, are divided into group 1 (CD1a, CD1b, and CD1c) and group 2 (CD1d). Although the role of CD1d-restricted natural killer T cells (NKT) in several tumor models has been well established, the contribution of group 1 CD1-restricted T cells in tumor immunity remains obscure due to the lack of group 1 CD1 expression in mice...
2016: Oncoimmunology
Seungkyu Choi, Jai Hyang Go, Eun Kyung Kim, Hojung Lee, Won Mi Lee, Chun-Sung Cho, Kyudong Han
Extranodal natural killer (NK)/T-cell lymphoma, nasal type (NKTCL), is a malignant disorder of cytotoxic lymphocytes of NK or T cells. It is an aggressive neoplasm with a very poor prognosis. Although extranodal NKTCL reportedly has a strong association with Epstein-Barr virus, the molecular pathogenesis of NKTCL has been unexplored. The recent technological advancements in next-generation sequencing (NGS) have made DNA sequencing cost- and time-effective, with more reliable results. Using the Ion Proton Comprehensive Cancer Panel, we sequenced 409 cancer-related genes to identify somatic mutations in five NKTCL tissue samples...
September 2016: Genomics & Informatics
John A Todd, Marina Evangelou, Antony J Cutler, Marcin L Pekalski, Neil M Walker, Helen E Stevens, Linsey Porter, Deborah J Smyth, Daniel B Rainbow, Ricardo C Ferreira, Laura Esposito, Kara M D Hunter, Kevin Loudon, Kathryn Irons, Jennie H Yang, Charles J M Bell, Helen Schuilenburg, James Heywood, Ben Challis, Sankalpa Neupane, Pamela Clarke, Gillian Coleman, Sarah Dawson, Donna Goymer, Katerina Anselmiova, Jane Kennet, Judy Brown, Sarah L Caddy, Jia Lu, Jane Greatorex, Ian Goodfellow, Chris Wallace, Tim I Tree, Mark Evans, Adrian P Mander, Simon Bond, Linda S Wicker, Frank Waldron-Lynch
BACKGROUND: Interleukin-2 (IL-2) has an essential role in the expansion and function of CD4+ regulatory T cells (Tregs). Tregs reduce tissue damage by limiting the immune response following infection and regulate autoreactive CD4+ effector T cells (Teffs) to prevent autoimmune diseases, such as type 1 diabetes (T1D). Genetic susceptibility to T1D causes alterations in the IL-2 pathway, a finding that supports Tregs as a cellular therapeutic target. Aldesleukin (Proleukin; recombinant human IL-2), which is administered at high doses to activate the immune system in cancer immunotherapy, is now being repositioned to treat inflammatory and autoimmune disorders at lower doses by targeting Tregs...
October 2016: PLoS Medicine
Martin R Goodier, Chiara Lusa, Sam Sherratt, Ana Rodriguez-Galan, Ron Behrens, Eleanor M Riley
Cross-linking of FcγRIII (CD16) by immune complexes induces antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells, contributing to control of intracellular pathogens; this pathway can also be targeted for immunotherapy of cancerous or otherwise diseased cells. However, downregulation of CD16 expression on activated NK cells may limit or regulate this response. Here, we report sustained downregulation of CD16 expression on NK cells in vivo after intramuscular (but not intranasal) influenza vaccination...
2016: Frontiers in Immunology
John F Trant, Namrata Jain, Delfina M Mazzuca, James T McIntosh, Bo Fan, S M Mansour Haeryfar, Sebastien Lecommandoux, Elizabeth R Gillies
Nanoassemblies presenting multivalent displays of biologically active carbohydrates are of significant interest for a wide array of biomedical applications ranging from drug delivery to immunotherapy. In this study, glycodendron-lipid hybrids were developed as a new and tunable class of dendritic amphiphiles. A modular synthesis was used to prepare dendron-lipid hybrids comprising distearylglycerol and 0 through 4th generation polyester dendrons with peripheral protected amines. Following deprotection of the amines, an isothiocyanate derivative of C-linked α-galactose (α-Gal) was conjugated to the dendron peripheries, affording amphiphiles with 1 to 16 α-Gal moieties...
October 14, 2016: Nanoscale
Xiao-Ping Wang, Qiao-Xia Wang, Huan-Ping Lin, Bing Xu, Qian Zhao, Kun Chen
Alpha-fetoprotein (AFP) is a marker of hepatocellular carcinoma (HCC) and serves as a target for immunotherapy. However, current treatments targeting AFP are not reproducible and do not provide complete protection against cancer. This issue may be solved by developing novel therapeutic vaccines with enhanced immunogenicity that could effectively target AFP-expressing tumors. In this study, we report construction of a therapeutic peptide vaccine by linking heat shock protein 70 (HSP70) functional peptide to the AFP epitope to obtain HSP70-P/AFP-P...
October 4, 2016: Oncotarget
Wei Li, Hongjia Yang, Dimiter S Dimitrov
CD16A (FcγRIIIA) is an activating receptor mostly expressed on natural killer (NK) cells and monocytes/macrophages. It can mediate antibody-dependent cell-mediated cytotoxicity (ADCC) through low-affinity interaction with human immunoglobulin G (IgG) Fc. It can also mediate cell lysis if NK cells are guided by bispecific killer cells engagers (BiKEs). BiKEs showed some success in clinical trials of cancer and are promising candidate therapeutics. However, currently reported BiKEs are based on antibody fragments (scFvs) of relatively large size...
October 3, 2016: Experimental and Molecular Pathology
Jun-Ying Du, Yi Liang, Jun-Fan Fang, Yong-Liang Jiang, Xiao-Mei Shao, Xiao-Fen He, Jian-Qiao Fang
Exogenous and endogenous opioids have been shown to modulate the immune system. Morphine-induced immunosuppression has been investigated extensively. However, the immune-regulating function of endogenous opioid peptides is unclear. The present study aimed to evaluate the difference in effects on cellular immune function between recombinant rat β-endorphin (β-EP; 50 µg/kg) and plant source morphine (10 mg/kg) via intraperitoneal injection treatment in a rat model of bone cancer pain. Walker 256 cells were injected into a tibial cavity injection to establish the bone cancer pain model...
October 2016: Experimental and Therapeutic Medicine
Susan J Lee, Ivan Borrello
Multiple myeloma (MM) is a hematologic cancer derived from malignant plasma cells within the bone marrow. Unlike most solid tumors, which originate from epithelial cells, the myeloma tumor is a plasma cell derived from the lymphoid cell lineage originating from a post-germinal B-cell. As such, the MM plasma cell represents an integral component of the immune system in terms of both antibody production and antigen presentation, albeit not efficiently. This fundamental difference has significant implications when one considers the implications of immunotherapy...
2016: Cancer Treatment and Research
Jae-Cheol Jo, Misung Kim, Yunsuk Choi, Hyun-Jung Kim, Ji Eun Kim, Seoung Wan Chae, Hawk Kim, Hee Jeong Cha
Programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) are new therapeutic targets in cancer immunotherapy. The aim of this study was to investigate the clinicopathological characteristics of PD-1 and PD-L1 expression in extranodal natural killer/T‑cell lymphoma, nasal type (ENKTL). We performed PD-1 and PD-L1 immunostaining in 79 ENKTL biopsy samples and retrospectively analyzed medical records of all 79 patients from four tertiary referral hospitals. The expression of PD-1 and PD-L1 by tumor cells and/or infiltrating immune cells was evaluated...
October 3, 2016: Annals of Hematology
H Kadara, M Choi, J Zhang, E P Cuentas, J R Canales, S G Gaffney, Z Zhao, C Behrens, J Fujimoto, C Chow, Y Yoo, N Kalhor, C Moran, D Rimm, S Swisher, D L Gibbons, J Heymach, E Kaftan, J P Townsend, T J Lynch, J Schlessinger, J Lee, R P Lifton, I I Wistuba, R S Herbst
BACKGROUND: Lung adenocarcinomas (LUADs) lead to the majority of deaths attributable to lung cancer. We performed whole-exome sequencing (WES) and immune profiling analyses of a unique set of clinically annotated early-stage LUADs to better understand the pathogenesis of this disease and identify clinically relevant molecular markers. METHODS: We performed WES of 108 paired stage I-III LUADs and normal lung tissues using the Illumina HiSeq 2000 platform. Ten immune markers (PD-L1, PD-1, CD3, CD4, CD8, CD45ro, CD57, CD68, FOXP3 and Granzyme B) were profiled by imaging-based immunohistochemistry in a subset of LUADs (n=92)...
September 29, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Lei Wang, Xiang Hu, Yingxin Xu, Zhong Liu
The purpose of this study was to investigate the effects of arsenic trioxide (As2O3) on the infiltration of regulatory T cells (Tregs) in the local lung metastasis of mouse colon cancer in vivo and the regulation of Tregs in cytokine-induced killer cells (CIKs) in vitro. A high Tregs infiltration mouse colon cancer lung metastasis model was established by intravenous injection of CT26 murine colon carcinoma cells. Tumor-bearing mice were randomly divided into three groups: control group, low-dose As2O3 group, and high-dose As2O3 group...
September 27, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Nazanin Nazari, Shirin Farjadian
BACKGROUND: HLA-G is a nonclassical HLA class I molecule which, when elevated in tumor cells, is one of the main factors involved in tumor evasion of immune responses including NK and T cells. OBJECTIVE: To evaluate the effect of HLA-G downregulation on NK cell cytotoxicity in tumor cell lines. METHODS: The expression level of HLA-G was measured by real-time PCR and flowcytometry after transfection of SKOV3 by shRNA.1, which targets specific sequences in exon 4, or shRNA...
September 2016: Iranian Journal of Immunology: IJI
Cheol-Hun Son, Hong-Rae Lee, Eun-Kyoung Koh, Dong-Yeok Shin, Jae-Ho Bae, Kwangmo Yang, You-Soo Park
Decitabine has been found to have anti-metabolic and anti-tumor activities in various tumor cells. Recently, the use of decitabine in combination with other conventional therapies reportedly resulted in improved anti-tumor activity against various tumors. Ionizing radiation (IR) is widely used as a cancer treatment. Decitabine and IR improve immunogenicity and susceptibility of tumor cells to immune cells by up-regulating the expression of various molecules such as major histocompatibility complex (MHC) class I; natural-killer group 2, member D (NKG2D) ligands; and co-stimulatory molecules...
September 27, 2016: Scientific Reports
Asma Beldi-Ferchiou, Marion Lambert, Stéphanie Dogniaux, Frédéric Vély, Eric Vivier, Daniel Olive, Stéphanie Dupuy, Frank Levasseur, David Zucman, Céleste Lebbé, Damien Sène, Claire Hivroz, Sophie Caillat-Zucman
Programmed Death-1 (PD-1), an inhibitory receptor expressed by activated lymphocytes, is involved in regulating T- and B-cell responses. PD-1 and its ligands are exploited by a variety of cancers to facilitate tumor escape through PD-1-mediated functional exhaustion of effector T cells. Here, we report that PD-1 is upregulated on Natural Killer (NK) cells from patients with Kaposi sarcoma (KS). PD-1 was expressed in a sub-population of activated, mature CD56dimCD16pos NK cells with otherwise normal expression of NK surface receptors...
September 20, 2016: Oncotarget
Foo Yew Liew, Jean-Philippe Girard, Heth Roderick Turnquist
Interleukin-33 (IL-33) - a member of the IL-1 family - was originally described as an inducer of type 2 immune responses, activating T helper 2 (TH2) cells and mast cells. Now, evidence is accumulating that IL-33 also potently stimulates group 2 innate lymphoid cells (ILC2s), regulatory T (Treg) cells, TH1 cells, CD8(+) T cells and natural killer (NK) cells. This pleiotropic nature is reflected in the role of IL-33 in tissue and metabolic homeostasis, infection, inflammation, cancer and diseases of the central nervous system...
September 19, 2016: Nature Reviews. Immunology
Zhen-Kui Wang, Li Xue, Tao Wang, Xiu-Jie Wang, Zhi-Qiang Su
Invariant natural killer T (iNKT) cells are a unique subset of T cells that have been implicated in inflammation, atopy, autoimmunity, infections, and cancer. Although iNKT cells have been extensively studied over the past decade, its role in the pathogenesis of ischemic brain injury is still largely unknown. In our study, we determined whether iNKT cells infiltration occur in a mouse model of permanent cerebral ischemia. C57BL6/J male mice were treated with either alpha-galactosylceramide (α-GalCer) or vehicle control before undergoing permanent middle cerebral artery occlusion (pMCAO)...
October 28, 2016: Neuroscience Letters
Kristina Berg Lorvik, Clara Hammarstrom, Marte Fauskanger, Ole Audun Werner Haabeth, Michael Zangani, Guttorm Haraldsen, Bjarne Bogen, Alexandre Corthay
Adoptive cell therapy (ACT) trials to date have focused on transfer of autologous tumor-specific cytotoxic CD8+ T cells, however, the potential of CD4+ T helper (Th) cells for ACT is gaining interest. While encouraging results have been reported with interferon-γ (IFNγ)-producing Th1 cells, tumor-specific Th2 cells have been largely neglected for ACT due to their reported tumor-promoting properties. In this study, we tested the efficacy of idiotype-specific Th2 cells for the treatment of mice with Major Histocompatibility Complex (MHC) class II-negative myeloma...
September 12, 2016: Cancer Research
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