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Memory t cell cancer

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https://www.readbyqxmd.com/read/28915554/resistance-to-ctla-4-checkpoint-inhibition-reversed-through-selective-elimination-of-granulocytic-myeloid-cells
#1
Paul E Clavijo, Ellen C Moore, Jianhong Chen, Ruth J Davis, Jay Friedman, Young Kim, Carter Van Waes, Zhong Chen, Clint T Allen
PURPOSE: Local immunosuppression remains a critical problem that limits clinically meaningful response to checkpoint inhibition in patients with head and neck cancer. Here, we assessed the impact of MDSC elimination on responses to CTLA-4 checkpoint inhibition. EXPERIMENTAL DESIGN: Murine syngeneic carcinoma immune infiltrates were characterized by flow cytometry. Granulocytic MDSCs (gMDSCs) were depleted and T-lymphocyte antigen-specific responses were measured...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912369/customized-viral-immunotherapy-for-hpv-associated-cancer
#2
Matthew J Atherton, Kyle B Stephenson, Jonathan Pol, Fuan Wang, Charles Lefebvre, David F Stojdl, Jake K Nikota, Anna Dvorkin-Gheva, Andrew Nguyen, Lan Chen, Stephanie Johnson-Obaseki, Patrick J Villeneuve, Jean-Simon Diallo, Jim Dimitroulakos, Yonghong Wan, Brian D Lichty
The viral transforming proteins E6 and E7 make human papilloma virus positive (HPV+) malignancies an attractive target for cancer immunotherapy. However, therapeutic vaccination exerts limited efficacy in the setting of advanced disease. We designed a strategy to induce substantial specific immune responses against multiple epitopes of E6 and E7 proteins based on an attenuated transgene from HPV serotypes 16 and 18 that is incorporated into MG1-Maraba virotherapy (MG1-E6E7). Mutations introduced to the transgene abrogate the ability of E6 and E7 to perturb p53 and retinoblastoma, respectively, while maintaining the ability to invoke tumor-specific, multi-functional CD8+ T-cell responses...
September 14, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28904691/il-21-augments-rapamycin-in-expansion-of-alpha-fetoprotein-antigen-specific-stem-cell-like-memory-t-cells-in-vitro
#3
Victor Tunje Jeza, Xiaoyi Li, Jun Chen, Zhihui Liang, Adem Onago Aggrey, Xiongwen Wu
INTRODUCTION: Alloreactive tumor specific T cells are important arsenals of the adaptive immune system in the fight against tumors. However, stem cell-like memory T cells (Tscm) provide the key to effective elimination of tumor cells. Methods for generating these T cell subsets already exist. However, they could be made more efficient. Further, they are expensive and unattainable to the resource poor laboratories. In this regard, we are hereby describing a novel in vitro allogeneic co-culture method for raising allo-restricted tumor specific Tscm cells that we developed...
2017: Pan African Medical Journal
https://www.readbyqxmd.com/read/28901740/inhibiting-metastasis-and-preventing-tumor-relapse-by-triggering-host-immunity-with-tumor-targeted-photodynamic-therapy-using-photosensitizer-loaded-functional-nanographenes
#4
Xinhe Yu, Duo Gao, Liquan Gao, Jianhao Lai, Chenran Zhang, Yang Zhao, Lijun Zhong, Bing Jia, Fan Wang, Xiaoyuan Chen, Zhaofei Liu
Effective cancer therapy depends not only on destroying the primary tumor, but also on conditioning the host immune system to recognize and eliminate residual tumor cells and prevent metastasis. In this study, a tumor integrin αvβ6-targeting peptide (the HK peptide)-functionalized graphene oxide (GO) was coated with a photosensitizer (HPPH). The resulting GO conjugate, GO(HPPH)-PEG-HK, was investigated whether it could destroy primary tumors and boost host antitumor immunity. We found that GO(HPPH)-PEG-HK exhibited significantly higher tumor uptake than GO(HPPH)-PEG and HPPH...
September 13, 2017: ACS Nano
https://www.readbyqxmd.com/read/28892469/de-novo-induction-of-intratumoral-lymphoid-structures-and-vessel-normalization-enhances-immunotherapy-in-resistant-tumors
#5
Anna Johansson-Percival, Bo He, Zhi-Jie Li, Alva Kjellén, Karen Russell, Ji Li, Irma Larma, Ruth Ganss
The tumor microenvironment confers profound resistance to anti-cancer immunotherapy. By targeting LIGHT, a member of the TNF superfamily of cytokines, to tumor vessels via a vascular targeting peptide (VTP), we developed a reagent with the dual ability to modulate the angiogenic vasculature and to induce tertiary lymphoid structures (TLSs). LIGHT-VTP triggered the influx of endogenous T cells into autochthonous or syngeneic tumors, which are resistant to immunotherapy. LIGHT-VTP in combination with checkpoint inhibition generated a large number of intratumoral effector and memory T cells with ensuing survival benefits, while the addition of anti-tumor vaccination achieved maximal therapeutic efficacy...
September 11, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28888485/immunobiology-of-the-il-15-il-15r%C3%AE-complex-as-an-antitumor-and-antiviral-agent
#6
REVIEW
Yin Guo, Liming Luan, Naeem K Patil, Edward R Sherwood
Interleukin (IL)-15 is essential for natural killer (NK), NKT and memory (m) CD8(+) T cell development and function, and is currently under investigation as an immunotherapeutic agent for the treatment of cancer. Recently, the creation of IL-15 superagonist by complexing IL-15 and its high affinity receptor alpha (IL-15 Rα) in solution, inspired by the natural trans-presentation of IL-15, advances the potential of IL-15-based tumor immunotherapy. IL-15 superagonist shows promising advantages over monomeric IL-15 such as sustaining high circulating concentrations due to prolonged half-life and more potently stimulating NK and CD8(+) T effector lymphocytes...
September 1, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28876947/integrin-assisted-t-cell-activation-on-nanostructured-hydrogels
#7
Judith Guasch, Christine A Muth, Jennifer Diemer, Hossein Riahinezhad, Joachim P Spatz
Adoptive cell therapy (ACT) has shown very promising results as treatment for cancer in a few clinical trials, such as the complete remissions of otherwise terminal leukemia patients. Nevertheless, the introduction of ACT into clinics requires overcoming not only medical but also technical challenges, such as the ex vivo expansion of large amounts of specific T-cells. Nanostructured surfaces represent a novel T-cell stimulation technique that enables us to fine-tune the density and orientation of activating molecules presented to the cells...
September 6, 2017: Nano Letters
https://www.readbyqxmd.com/read/28874354/the-inhibitory-signaling-receptor-protocadherin-18-regulates-tumor-infiltrating-cd8-t-cell-function
#8
Alan B Frey
Cancers are infiltrated with antitumor CD8+ T cells that arise during tumor growth, but are defective in effector phase functions because of the suppressive microenvironment. The reactivation of TILs can result in tumor destruction, showing that lytic dysfunction in CD8+ tumor-infiltrating lymphocytes (TILs) permits tumor growth. Like all memory T cells, TILs express inhibitory signaling receptors (aka checkpoint inhibitor molecules) that downregulate TCR-mediated signal transduction upon TIL interaction with cells expressing cognate ligands, thereby restricting cell activation and preventing the effector phase...
September 5, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28871164/tumor-infiltrating-cd45ro-memory-t-lymphocytes-predict-favorable-clinical-outcome-in-solid-tumors
#9
Guoming Hu, Shimin Wang
The prognostic role of tumor-infiltrating CD45RO(+) memory T lymphocytes (CD45RO(+) T cells) in human solid tumors remains controversial. Herein, we conducted a meta-analysis including 25 published studies with 4720 patients identified from PubMed and EBSCO to assess the prognostic impact of tumor-infiltrating CD45RO(+) T cells in human solid tumors. We found that CD45RO(+) T cell infiltration was significantly associated with improved overall survival (OS) and disease-free survival (DFS) in all types of solid tumors...
September 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28866656/immune-checkpoint-inhibitors-in-cancer-therapy
#10
Eika S Webb, Peng Liu, Renato Baleeiro, Nicholas R Lemoine, Ming Yuan, Yao-He Wang
In recent years immune checkpoint inhibitors have garnered attention as being one of the most promising types of immunotherapy on the horizon. There has been particular focus on the immune checkpoint molecules, cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1) which have been shown to have potent immunomodulatory effects through their function as negative regulators of T cell activation. CTLA-4, through engagement with its ligands B7-1 (CD80) and B7-2 (CD86), plays a pivotal role in attenuating the activation of naïve and memory T cells...
September 3, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28861081/14%C3%A2-years-after-discovery-clinical-follow-up-on-15-patients-with-inducible-co-stimulator-deficiency
#11
Johanna Schepp, Janet Chou, Andrea Skrabl-Baumgartner, Peter D Arkwright, Karin R Engelhardt, Sophie Hambleton, Tomohiro Morio, Ekkehard Röther, Klaus Warnatz, Raif Geha, Bodo Grimbacher
BACKGROUND: Inducible co-stimulator (ICOS) deficiency was the first monogenic defect reported to cause common variable immunodeficiency (CVID)-like disease in 2003. Since then, 16 patients have been reported worldwide with an increasing range of clinical phenotypes. OBJECTIVE: We sought to compare the clinical and immunological phenotype and provide clinical follow-up and therapeutic approaches for treating ICOS-deficient patients. METHODS: We describe the clinical and laboratory data of 15 patients with available clinical data...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28855514/hit-and-run-programming-of-therapeutic-cytoreagents-using-mrna-nanocarriers
#12
H F Moffett, M E Coon, S Radtke, S B Stephan, L McKnight, A Lambert, B L Stoddard, H P Kiem, M T Stephan
Therapies based on immune cells have been applied for diseases ranging from cancer to diabetes. However, the viral and electroporation methods used to create cytoreagents are complex and expensive. Consequently, we develop targeted mRNA nanocarriers that are simply mixed with cells to reprogram them via transient expression. Here, we describe three examples to establish that the approach is simple and generalizable. First, we demonstrate that nanocarriers delivering mRNA encoding a genome-editing agent can efficiently knock-out selected genes in anti-cancer T-cells...
August 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/28851693/the-antitumor-effects-of-vaccine-activated-cd8-t-cells-associate-with-weak-tcr-signaling-and-induction-of-stem-like-memory-t-cells
#13
Sha Wu, Wei Zhu, Yibing Peng, Lan Wang, Yuang Hong, Lei Huang, Dayong Dong, Junping Xie, Todd Merchen, Edward Kruse, Zong Sheng Guo, David Bartlett, Ning Fu, Yukai He
To understand why vaccine-activated tumor-specific T cells often fail to generate antitumor effects, we studied two alpha-fetoprotein-specific CD8+ T cells (Tet499 and Tet212) that had different antitumor effects. We found that Tet499 required high antigen doses for re-activation, but could survive persistent antigen stimulation and maintain their effector functions. In contrast, Tet212 had a low threshold of re-activation, but underwent exhaustion and apoptosis in the presence of persistent antigen. In vivo, Tet499 cells expanded more than Tet212 upon re-encountering antigen and generated stronger antitumor effects...
August 29, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28843293/langerhans-cells-orchestrate-tfh-dependent-humoral-immunity
#14
Trupti Vardam, Niroshana Anandasabapathy
T follicular helper cells contribute to the development of long-lasting humoral immunity by germinal center formation. Somatic hypermutation and affinity maturation take place in germinal centers leading to the generation of memory B cells and plasma cells. As such, T follicular helper cells impact immunodeficiencies, autoimmunity, and cancer. This necessitates further understanding of how T follicular helper cells are regulated in health and disease. The current study by Levin et al. builds on prior work to further substantiate a critical role for skin migratory dendritic cells and in particular Langerhans cells at governing T follicular helper and germinal center formation after intradermal immunization with HIV p24-coated polylactic acid nanoparticles...
September 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28817117/increased-tumor-infiltrating-cd45ra-ccr7-regulatory-t-cell-subset-with-immunosuppressive-properties-foster-gastric-cancer-progress
#15
Fang-Yuan Mao, Hui Kong, Yong-Liang Zhao, Liu-Sheng Peng, Weisan Chen, Jin-Yu Zhang, Ping Cheng, Ting-Ting Wang, Yi-Pin Lv, Yong-Sheng Teng, Xiao-Long Fu, Yu-Gang Liu, Xiao-Long Wu, Chuan-Jie Hao, Nan You, Ping Luo, Pei-Wu Yu, Quan-Ming Zou, Gang Guo, Yuan Zhuang
Regulatory T cells (Tregs) are major components of tumor-infiltrating immune cells with potent immunosuppressive properties in gastric cancer (GC) microenvironment. However, different subsets of the Tregs and their relevance to GC are unknown. Here, we found that patients with GC showed a significantly higher Tregs infiltration in tumors, and CD45RA(-)CCR7(-) Treg subset constituted most tumor-infiltrating Tregs. Tumor-infiltrating CD45RA(-)CCR7(-) Treg subset with an effector/memory phenotype accumulated in tumors and expressed low level of HLA-DR...
August 17, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28790368/signs-of-innate-immune-activation-and-premature-immunosenescence-in-psoriasis-patients
#16
Liisi Šahmatova, Elena Sügis, Marina Šunina, Helen Hermann, Ele Prans, Maire Pihlap, Kristi Abram, Ana Rebane, Hedi Peterson, Pärt Peterson, Külli Kingo, Kai Kisand
Psoriasis is a chronic inflammatory disease that affects skin and is associated with systemic inflammation and many serious comorbidities ranging from metabolic syndrome to cancer. Important discoveries about psoriasis pathogenesis have enabled the development of effective biological treatments blocking the T helper 17 pathway. However, it has not been settled whether psoriasis is a T cell-mediated autoimmune disease or an autoinflammatory disorder that is driven by exaggerated innate immune signalling. Our comparative gene expression and hierarchical cluster analysis reveal important gene circuits involving innate receptors...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28765518/characterization-of-infiltrating-lymphocytes-in-human-benign-and-malignant-prostate-tissue
#17
Emelie Rådestad, Lars Egevad, Carl Jorns, Jonas Mattsson, Berit Sundberg, Silvia Nava, Bo-Göran Ericzon, Lars Henningsohn, Victor Levitsky, Michael Uhlin
Immune checkpoint blockade has shown promising results in numerous cancer types. However, in prostate cancer (PC), absent or limited responses have been reported. To investigate further, we compared the phenotype of infiltrating T-cells isolated from prostate tissue from patients with PC (n = 5), benign prostatic hyperplasia (BPH) (n = 27), BPH with concurrent PC (n = 4) and controls (n = 7). The majority of T-cells were CD8+ and had a CCR7-CD45RO+ effector memory phenotype. However, the yield of T-cells isolated from PC lesions was on average 20-fold higher than that obtained from control prostates...
July 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28761757/mechanisms-of-action-and-rationale-for-the-use-of-checkpoint-inhibitors-in-cancer
#18
REVIEW
Clemence Granier, Eleonore De Guillebon, Charlotte Blanc, Helene Roussel, Cecile Badoual, Elia Colin, Antonin Saldmann, Alain Gey, Stephane Oudard, Eric Tartour
The large family of costimulatory molecules plays a crucial role in regulation of the immune response. These molecules modulate TCR signalling via phosphorylation cascades. Some of the coinhibitory members of this family, such as PD-1 and CTLA-4, already constitute approved targets in cancer therapy and, since 2011, have opened a new area of antitumour immunotherapy. Many antibodies targeting other inhibitory receptors (Tim-3, VISTA, Lag-3 and so on) or activating costimulatory molecules (OX40, GITR and so on) are under evaluation...
2017: ESMO Open
https://www.readbyqxmd.com/read/28759630/c77g-in-ptprc-cd45-is-no-risk-allele-for-ovarian-cancer-but-associated-with-less-aggressive-disease
#19
Johannes Landskron, Sigrid M Kraggerud, Elisabeth Wik, Anne Dørum, Merete Bjørnslett, Espen Melum, Øystein Helland, Line Bjørge, Ragnhild A Lothe, Helga B Salvesen, Kjetil Taskén
The pan lymphocyte marker CD45 exists in various isoforms arising from alternative splicing of the exons 4, 5 and 6. While naïve T cells express CD45RA translated from an mRNA containing exon 4, exons 4-6 are spliced out to encode the shorter CD45R0 in antigen-experienced effector/memory T cells. The SNP C77G (rs17612648) is located in exon 4 and blocks the exon's differential splicing from the pre-mRNA, enforcing expression of CD45RA. Several studies have linked C77G to autoimmune diseases but lack of validation in other cohorts has left its role elusive...
2017: PloS One
https://www.readbyqxmd.com/read/28755541/vaccines-targeting-helper-t-cells-for-cancer-immunotherapy
#20
REVIEW
Marit Melssen, Craig L Slingluff
There are compelling arguments for designing cancer vaccines specifically to induce CD4(+) helper T cell responses. Recent studies highlight the crucial role of proliferating, activated effector memory Th1 CD4(+) T cells in effective antitumor immunity and reveal that CD4(+) T cells induce more durable immune-mediated tumor control than CD8(+) T cells. CD4(+) T cells promote antitumor immunity by numerous mechanisms including enhancing antigen presentation, co-stimulation, T cell homing, T cell activation, and effector function...
July 26, 2017: Current Opinion in Immunology
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