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https://www.readbyqxmd.com/read/29656492/pd-1-blockade-cellular-vesicles-for-cancer-immunotherapy
#1
Xudong Zhang, Chao Wang, Jinqiang Wang, Quanyin Hu, Benjamin Langworthy, Yanqi Ye, Wujin Sun, Jing Lin, Tianfu Wang, Jason Fine, Hao Cheng, Gianpietro Dotti, Peng Huang, Zhen Gu
Cancer cells resist to the host immune antitumor response via multiple suppressive mechanisms, including the overexpression of PD-L1 that exhausts antigen-specific CD8+ T cells through PD-1 receptors. Checkpoint blockade antibodies against PD-1 or PD-L1 have shown unprecedented clinical responses. However, limited host response rate underlines the need to develop alternative engineering approaches. Here, engineered cellular nanovesicles (NVs) presenting PD-1 receptors on their membranes, which enhance antitumor responses by disrupting the PD-1/PD-L1 immune inhibitory axis, are reported...
April 14, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29655570/interleukin-7-enhances-anti-tumor-activity-of-cd8-t-cells-in-patients-with-hepatocellular-carcinoma
#2
Dengke Teng, Lei Ding, Bo Cai, Qiang Luo, Hui Wang
Interleukin (IL)-7 stimulation improves virus- and tumor-specific CD8+ T cell responses. However, the role of IL-7 in modulation of dysfunctional CD8+ T cells in hepatocellular carcinoma (HCC) was not completely understood. In this study, a total of 37 HLA-A2 restricted patients with HCC and 16 healthy individuals were enrolled. IL-7 expression and its receptor α chain CD127 level was measured. The regulatory activity of IL-7 to peripheral and liver-resident CD8+ T cells was investigated in co-culture systems which were directly or indirectly contacted with HCC cell line HepG2 in vitro...
April 11, 2018: Cytokine
https://www.readbyqxmd.com/read/29653410/rescue-of-iciks-transfer-from-pd-1-pd-l1-immune-inhibition-in-patients-with-resectable-tongue-squamous-cell-carcinoma-tscc
#3
Xiaofeng Huang, Jing Zhang, Xiaolong Li, Hongxing Huang, Ying Liu, Mei Yu, Yan Zhang, Hua Wang
OBJECTIVES: The purpose of this study is to evaluate the therapeutic efficacy and the role of PD-1/PD-L1 pathway in tongue squamous cell carcinoma (TSCC) patients treated with radical operation combined with chemotherapy and improving cytokine induced killer cells (iCIKs) transfer. METHODS: Thirteen patients who received radical resection and chemotherapy were enrolled in this study. PD-1/PD-L1 expression was evaluated in TSCC patients. ICIKs were cultured from patient-derived peripheral blood mononuclear cells (PBMCs) in vitro...
April 10, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29652930/tissue-maintenance-of-cmv-specific-inflationary-memory-t-cells-by-il-15
#4
Nicolas S Baumann, Nicole Torti, Suzanne P M Welten, Isabel Barnstorf, Mariana Borsa, Katharina Pallmer, Jennifer D Oduro, Luka Cicin-Sain, Koichi Ikuta, Burkhard Ludewig, Annette Oxenius
Cytomegalovirus (CMV) infection induces an atypical CD8 T cell response, termed inflationary, that is characterised by accumulation and maintenance of high numbers of effector memory like cells in circulation and peripheral tissues-a feature being successfully harnessed for vaccine purposes. Although stability of this population depends on recurrent antigen encounter, the requirements for prolonged survival in peripheral tissues remain unknown. Here, we reveal that murine CMV-specific inflationary CD8 T cells are maintained in an antigen-independent manner and have a half-life of 12 weeks in the lung tissue...
April 13, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29652910/elderly-dendritic-cells-respond-to-lps-ifn-%C3%AE-and-cd40l-stimulation-despite-incomplete-maturation
#5
Joanne K Gardner, Scott M J Cornwall, Arthur W Musk, John Alvarez, Cyril D S Mamotte, Connie Jackaman, Anna K Nowak, Delia J Nelson
There is evidence that dendritic cells (DCs) undergo age-related changes that modulate their function with their key role being priming antigen-specific effector T cells. This occurs once DCs develop into antigen-presenting cells in response to stimuli/danger signals. However, the effects of aging on DC responses to bacterial lipopolysaccharide (LPS), the pro-inflammatory cytokine interferon (IFN)-γ and CD40 ligand (CD40L) have not yet been systematically evaluated. We examined responses of blood myeloid (m)DC1s, mDC2s, plasmacytoid (p)DCs, and monocyte-derived DCs (MoDCs) from young (21-40 years) and elderly (60-84 years) healthy human volunteers to LPS/IFN-γ or CD40L stimulation...
2018: PloS One
https://www.readbyqxmd.com/read/29652096/rapid-reconstitution-of-cmv-specific-t-cells-after-stem-cell-transplantation
#6
Thomas Widmann, Urban Sester, Tina Schmidt, Barbara C Gärtner, Jörg Schubert, Michael Pfreundschuh, Martina Sester
OBJECTIVE: As reconstitution of virus-specific T-cells is critical to control CMV-viremia following stem-cell transplantation (SCT) we characterized the dynamics in CMV-specific T-cell reconstitution after SCT. METHODS: CMV-specific T-cells from 51 SCT-recipients were prospectively quantified and phenotypically characterised by intracellular cytokine-staining after specific stimulation and HLA class-I specific pentamers using flow-cytometry. RESULTS: CMV-specific CD4 T-cells reconstituted after a median of 2...
April 13, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29650230/production-of-spliced-peptides-by-the-proteasome
#7
Nathalie Vigneron, Vincent Stroobant, Violette Ferrari, Joanna Abi Habib, Benoit J Van den Eynde
CD8+ cytolytic T lymphocytes are essential players of anti-tumor immune responses. On tumors, they recognize peptides of about 8-to-10 amino acids that generally result from the degradation of cellular proteins by the proteasome. Until a decade ago, these peptides were thought to solely correspond to linear fragments of proteins that were liberated after the hydrolysis of the peptide bonds located at their extremities. However, several examples of peptides containing two fragments originally distant in the protein sequence challenged this concept and demonstrated that proteasome could also splice peptides together by creating a new peptide bond between two distant fragments...
April 9, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29649617/reversal-of-t-cell-exhaustion-by-the-first-donor-lymphocyte-infusion-is-associated-with-the-persistently-effective-anti-leukemic-responses-in-patients-with-relapsed-aml-after-allo-hsct
#8
Long Liu, Ying-Jun Chang, Lan-Ping Xu, Xiao-Hui Zhang, Yu Wang, Kai-Yan Liu, Xiao-Jun Huang
Donor lymphocyte infusion is an effective approach to treat acute myeloid leukemia (AML) relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) that significantly improves the survival of relapsed patients. However, the mechanism of an effective anti-leukemic response following DLI in AML relapse remains elusive. Here, we investigated the role of T cell exhaustion in AML relapse after allo-HSCT in prospective cohorts of 41 patients with the first AML relapse and 41 non-relapsed AML controls after allo-HSCT and determined whether DLI exerts effective anti-leukemic effects by reversing T cell exhaustion in the relapsed cohorts by detecting the phenotypes and functions of T cells using flow cytometry...
April 9, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29649593/gold-nanoparticles-conjugating-recombinant-influenza-hemagglutinin-trimers-and-flagellin-enhanced-mucosal-cellular-immunity
#9
Chao Wang, Wandi Zhu, Yuan Luo, Bao-Zhong Wang
The immunogenicity of subunit vaccines can be augmented by formulating them into nanoparticles. We conjugated recombinant trimetric influenza A/Aichi/2/68(H3N2) hemagglutinin (HA) onto functionalized gold nanoparticles (AuNPs) surfaces in a repetitive, oriented configuration. To further improve the immunogenicity, we generated Toll-like receptor 5 (TLR5) agonist flagellin (FliC)-coupled AuNPs as particulate adjuvants. Intranasal immunizations with an AuNP-HA and AuNP-FliC particle mixture elicited strong mucosal and systemic immune responses that protected hosts against lethal influenza challenges...
April 9, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29649077/circulating-cxcr5-expressing-cd8-t-cells-are-major-producers-of-il-21-and-associate-with-limited-hiv-replication
#10
Federico Perdomo-Celis, Natalia A Taborda, Maria T Rugeles
BACKGROUND: Despite advances made with the highly active anti-retroviral therapy (HAART) in the control of the human immunodeficiency virus 1 (HIV) infection, a cure has not been achieved due to the persistence of viral reservoirs. The major HIV reservoirs remain in the lymphoid follicles due to, among other factors, the partial absence of CD8T-cells in these structures. Recently, lymphoid follicle-confined and circulating CD8T-cells expressing the C-X-C chemokine receptor type 5 (CXCR5) were described, possessing antiviral mechanisms which could help to control HIV replication...
April 10, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29648684/inhibitory-receptor-expression-on-t-cells-as-marker-of-disease-activity-and-target-to-regulate-effector-cellular-responses-in-rheumatoid-arthritis
#11
Luisina I Onofrio, Estefania R Zacca, Paola Ferrero, Cristina Acosta, Eduardo Mussano, Laura Onetti, Isaac Cadile, M Victoria Gazzoni, Raúl Jurado, Jimena Tosello Boari, Maria C Ramello, Carolina L Montes, Adriana Gruppi, Eva V Acosta Rodríguez
OBJECTIVE: Inhibitory receptors (IRs) are essential to regulate effector immune responses and may play critical roles during autoimmune diseases. In Rheumatoid Arthritis (RA), we evaluated whether IR expression on T cells showed correlation with immune activation, disease activity and response to treatment as well as if IR-mediated pathways were functional. METHODS: By flow cytometry, we performed extensive phenotypic and functional evaluation of CD4+ and CD8+ T cells from blood and synovial fluid of RA patients ex vivo and after culture...
April 12, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29648517/preliminary-evidence-of-reductive-stress-in-human-cytotoxic-t-cells-following-exercise
#12
Alex James Wadley, Adrian Holliday, Rhys G Morgan, Kate J Heesom, Sarah Aldred, Derek M Peters, Allain A Bueno, Steven J Coles
This study investigated immunophenotypic differences in intracellular thiol redox state of peripheral blood mononuclear cells (PBMCs) isolated from trained (TR, n=9, mean {plus minus} SD: age 28 {plus minus} 5 years; BMI 23.2 {plus minus} 2.6 kg·m2 ; VO2max 56.9 {plus minus} 6.1 ml·kg-1 ·min-1 ) and recreationally active (RA, n=11, mean {plus minus} SD: age 27 {plus minus} 6 years; BMI 24.2 {plus minus} 3.7 kg·m2 ; VO2max 45.1 {plus minus} 6.4 ml·kg-1 ·min-1 ) participants before and after a maximal aerobic exercise tolerance test...
April 12, 2018: Journal of Applied Physiology
https://www.readbyqxmd.com/read/29644653/specific-blockade-cd73-alters-the-exhausted-phenotype-of-t-cells-in-head-and-neck-squamous-cell-carcinoma
#13
Wei-Wei Deng, Yi-Cun Li, Si-Rui Ma, Liang Mao, Guang-Tao Yu, Lin-Lin Bu, Ashok B Kulkarni, Wen-Feng Zhang, Zhi-Jun Sun
The adenosine-induced immunosuppression hampers the immune response toward tumor cells and facilitates the tumor cells to evade immunosurveillance. CD73, an ecto-5-nucleotidase, is the ectoenzyme dephosphorylating extracellular AMP to adenosine. Here, using immunocompetent transgenic head and neck squamous cell carcinoma (HNSCC) mouse model, immune profiling showed high expression of CD73 on CD4+ and CD8+ T cells was associated with an 'exhausted' phenotype. Further, treatment with anti-CD73 monoclonal antibody (mAb) significantly blunted the tumor growth in the mouse model, and the blockade of CD73 reversed the 'exhausted' phenotype of CD4+ and CD8+ T cells through downregulation of total expression of PD-1 and CTLA-4 on T cells...
April 12, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29644213/immunotherapy-plus-cryotherapy-potential-augmented-abscopal-effect-for-advanced-cancers
#14
REVIEW
Joe Abdo, David L Cornell, Sumeet K Mittal, Devendra K Agrawal
Since the 1920s the gold standard for treating cancer has been surgery, which is typically preceded or followed with chemotherapy and/or radiation, a process that perhaps contributes to the destruction of a patient's immune defense system. Cryosurgery ablation of a solid tumor is mechanistically similar to a vaccination where hundreds of unique antigens from a heterogeneous population of tumor cells derived from the invading cancer are released. However, releasing tumor-derived self-antigens into circulation may not be sufficient enough to overcome the checkpoint escape mechanisms some cancers have evolved to avoid immune responses...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29643992/description-of-organ-specific-phenotype-and-functional-characteristics-of-tissue-resident-lymphocytes-from-liver-transplantation-donor-and-research-on-immune-tolerance-mechanism-of-liver
#15
Yunpeng Shi, Ping Zhang, Guangyi Wang, Xingkai Liu, Xiaodong Sun, Xin Zhang, Haijun Li, Jun Qi, Lei Ding, Ting Li, Ruoyan Zhang, Yuguo Chen, Jianpeng Zhou, Guoyue Lv, Zhengkun Tu
Aim: Prior to transplantation, Donation after Cardiac Death (DCD) liver transplantation livers are perfused with preservation solution. Therefore, this provides an abundant source of human liver lymphocytes, as well as mesenteric lymph node and spleen for the study of lymphocyte subset diversity in the peripheral blood, lymph node, spleen and liver. Methods: Lymphocyte subsets were isolated and purified from peripheral blood, lymph node, spleen and liver perfusion, the phenotypic and functional analysis of the tissue resident lymphocyte were performed by flow cytometry...
March 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29643246/the-dynamics-of-siv-2-ltr-circles-in-the-presence-and-absence-of-cd8-cells
#16
Benjamin B Policicchio, Erwing Fabian Cardozo, Paola Sette, Cuiling Xu, George Haret-Richter, Tammy Dunsmore, Cristian Apetrei, Ivona Pandrea, Ruy M Ribeiro
CD8+ cells play a key role in HIV/SIV infection, but their specific mechanism(s) of action in controlling the virus are unclear. 2-LTR circles are extrachromosomal products generated upon failed integration of HIV/SIV. To understand the specific effects of CD8+ cells on infected cells, we analyzed the dynamics of 2-LTR circles in SIVmac251-infected rhesus macaques (RM) treated with an integrase inhibitor (INT). Twenty RMs underwent CD8+ cell depletion, received RAL monotherapy or a combination of both. Blood, lymph nodes (LNs) and gut biopsies were routinely sampled...
April 11, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29643245/recombinant-porcine-reproductive-and-respiratory-syndrome-virus-expressing-membrane-bound-il-15-as-immunomodulatory-adjuvant-enhances-nk-and-%C3%AE-%C3%AE-t-cell-responses-and-confers-heterologous-protection
#17
Qian M Cao, Yan-Yan Ni, Dianjun Cao, Debin Tian, Danielle M Yugo, C Lynn Heffron, Christopher Overend, Sakthivel Subramaniam, Adam J Rogers, Nicholas Catanzaro, Tanya LeRoith, Paul C Roberts, Xiang-Jin Meng
Cytokines are often used as adjuvants to improve vaccine immunogenicity, since they are important in initiating and shaping the immune response. The available commercial modified live-attenuated vaccines (MLVs) against porcine reproductive and respiratory syndrome virus (PRRSV) are unable to mount sufficient heterologous protection, as they typically induce weak innate and inadequate T cell responses. In this study, we investigated the immunogenicity and vaccine efficacy of recombinant PRRSV MLVs incorporated with porcine cytokine IL-15 or IL-18 gene fusing to a glycophosphatidylinositol (GPI) modification signal that can anchor the cytokines to cell membrane...
April 11, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29643229/t-cell-induced-csf1-promotes-melanoma-resistance-to-pd1-blockade
#18
Natalie J Neubert, Martina Schmittnaegel, Natacha Bordry, Sina Nassiri, Noémie Wald, Christophe Martignier, Laure Tillé, Krisztian Homicsko, William Damsky, Hélène Maby-El Hajjami, Irina Klaman, Esther Danenberg, Kalliopi Ioannidou, Lana Kandalaft, George Coukos, Sabine Hoves, Carola H Ries, Silvia A Fuertes Marraco, Periklis G Foukas, Michele De Palma, Daniel E Speiser
Colony-stimulating factor 1 (CSF1) is a key regulator of monocyte/macrophage differentiation that sustains the protumorigenic functions of tumor-associated macrophages (TAMs). We show that CSF1 is expressed in human melanoma, and patients with metastatic melanoma have increased CSF1 in blood compared to healthy subjects. In tumors, CSF1 expression correlated with the abundance of CD8+ T cells and CD163+ TAMs. Human melanoma cell lines consistently produced CSF1 after exposure to melanoma-specific CD8+ T cells or T cell-derived cytokines in vitro, reflecting a broadly conserved mechanism of CSF1 induction by activated CD8+ T cells...
April 11, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29643193/cutting-edge-protection-by-antiviral-memory-cd8-t-cells-requires-rapidly-produced-antigen-in-large-amounts
#19
Sanda Remakus, Xueying Ma, Lingjuan Tang, Ren-Huan Xu, Cory Knudson, Carolina R Melo-Silva, Daniel Rubio, Yin-Ming Kuo, Andrew Andrews, Luis J Sigal
Numerous attempts to produce antiviral vaccines by harnessing memory CD8 T cells have failed. A barrier to progress is that we do not know what makes an Ag a viable target of protective CD8 T cell memory. We found that in mice susceptible to lethal mousepox (the mouse homolog of human smallpox), a dendritic cell vaccine that induced memory CD8 T cells fully protected mice when the infecting virus produced Ag in large quantities and with rapid kinetics. Protection did not occur when the Ag was produced in low amounts, even with rapid kinetics, and protection was only partial when the Ag was produced in large quantities but with slow kinetics...
April 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29643190/peptide-vaccine-formulation-controls-the-duration-of-antigen-presentation-and-magnitude-of-tumor-specific-cd8-t-cell-response
#20
Hiep Khong, Annika Volmari, Meenu Sharma, Zhimin Dai, Chinonye S Imo, Yared Hailemichael, Manisha Singh, Derek T Moore, Zhilan Xiao, Xue-Fei Huang, Thomas D Horvath, David H Hawke, Willem W Overwijk
Despite remarkable progresses in vaccinology, therapeutic cancer vaccines have not achieved their full potential. We previously showed that an excessively long duration of Ag presentation critically reduced the quantity and quality of vaccination-induced T cell responses and subsequent antitumor efficacy. In this study, using a murine model and tumor cell lines, we studied l-tyrosine amino acid-based microparticles as a peptide vaccine adjuvant with a short-term Ag depot function for the induction of tumor-specific T cells...
April 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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