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Anti-tumor T cell response

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https://www.readbyqxmd.com/read/28922374/fractional-laser-exposure-induces-neutrophil-infiltration-n1-phenotype-into-the-tumor-and-stimulates-systemic-anti-tumor-immune-response
#1
Masayoshi Kawakubo, Shadmehr Demehri, Dieter Manstein
BACKGROUND: Ablative fractional photothermolysis (aFP) using a CO2 laser generates multiple small diameter tissue lesions within the irradiation field. aFP is commonly used for a wide variety of dermatological indications, including treatment of photodamaged skin and dyschromia, drug delivery and modification of scars due to acne, surgical procedures and burns. In this study we explore the utility of aFP for treating oncological indications, including induction of local tumor regression and inducing anti-tumor immunity, which is in marked contrast to current indications of aFP...
2017: PloS One
https://www.readbyqxmd.com/read/28920005/the-frequency-of-neoantigens-per-somatic-mutation-rather-than-overall-mutational-load-or-number-of-predicted-neoantigens-per-se-is-a-prognostic-factor-in-ovarian-clear-cell-carcinoma
#2
Hirokazu Matsushita, Kosei Hasegawa, Katsutoshi Oda, Shogo Yamamoto, Akira Nishijima, Yuichi Imai, Kayo Asada, Yuji Ikeda, Takahiro Karasaki, Keiichi Fujiwara, Hiroyuki Aburatani, Kazuhiro Kakimi
Neoantigens derived from tumor-specific somatic mutations are excellent targets for anti-tumor immune responses. In ovarian clear cell carcinoma (OCCC), checkpoint blockade yields durable responses in a subset of patients. To approach the question of why only some patients respond, we first investigated neoantigen loads and immune signatures using exome sequencing and expression array data for 74 OCCC patients treated conventionally. Neither the number of missense mutations nor total predicted neoantigens assessed in the tumor correlated with clinical outcomes...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28920002/ep4-antagonism-by-e7046-diminishes-myeloid-immunosuppression-and-synergizes-with-treg-reducing-il-2-diphtheria-toxin-fusion-protein-in-restoring-anti-tumor-immunity
#3
Diana I Albu, Zichun Wang, Kuan-Chun Huang, Jiayi Wu, Natalie Twine, Sarah Leacu, Christy Ingersoll, Lana Parent, Winnie Lee, Diana Liu, Renee Wright-Michaud, Namita Kumar, Galina Kuznetsov, Qian Chen, Wanjun Zheng, Kenichi Nomoto, Mary Woodall-Jappe, Xingfeng Bao
Reprogramming of immunosuppressive tumor microenvironment (TME) by targeting alternatively activated tumor associated macrophages (M2TAM), myeloid-derived suppressor cells (MDSC), and regulatory T cells (Tregs), represents a promising strategy for developing novel cancer immunotherapy. Prostaglandin E2 (PGE2), an arachidonic acid pathway metabolite and mediator of chronic inflammation, has emerged as a powerful immunosuppressor in the TME through engagement with one or more of its 4 receptors (EP1-EP4). We have developed E7046, an orally bioavailable EP4-specific antagonist and show here that E7046 has specific and potent inhibitory activity on PGE2-mediated pro-tumor myeloid cell differentiation and activation...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28920001/zoledronic-acid-inhibits-nfat-and-il-2-signaling-pathways-in-regulatory-t-cells-and-diminishes-their-suppressive-function-in-patients-with-metastatic-cancer
#4
Dhifaf Sarhan, Caroline Leijonhufvud, Shannon Murray, Kristina Witt, Christina Seitz, Majken Wallerius, Hanjing Xie, Anders Ullén, Ulrika Harmenberg, Elisabet Lidbrink, Charlotte Rolny, John Andersson, Andreas Lundqvist
Regulatory T cells (Treg) suppress anti-tumor immune responses and their infiltration in the tumor microenvironment is associated with inferior prognosis in cancer patients. Thus, in order to enhance anti-tumor immune responses, selective depletion of Treg is highly desired. We found that treatment with zoledronic acid (ZA) resulted in a selective decrease in the frequency of Treg that was associated with a significant increase in proliferation of T cells and natural killer (NK) cells in peripheral blood of patients with metastatic cancer...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919885/trypanosoma-cruzi-evades-the-complement-system-as-an-efficient-strategy-to-survive-in-the-mammalian-host-the-specific-roles-of-host-parasite-molecules-and-trypanosoma-cruzi-calreticulin
#5
REVIEW
Galia Ramírez-Toloza, Arturo Ferreira
American Trypanosomiasis is an important neglected reemerging tropical parasitism, infecting about 8 million people worldwide. Its agent, Trypanosoma cruzi, exhibits multiple mechanisms to evade the host immune response and infect host cells. An important immune evasion strategy of T. cruzi infective stages is its capacity to inhibit the complement system activation on the parasite surface, avoiding opsonizing, immune stimulating and lytic effects. Epimastigotes, the non-infective form of the parasite, present in triatomine arthropod vectors, are highly susceptible to complement-mediated lysis while trypomastigotes, the infective form, present in host bloodstream, are resistant...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28918908/macrophage-biology-plays-a-central-role-during-ionizing-radiation-elicited-tumor-response
#6
REVIEW
Qiuji Wu, Awatef Allouch, Isabelle Martins, Nazanine Modjtahedi, Eric Deutsch, Jean-Luc Perfettini
Radiation therapy is one of the major therapeutic modalities for most solid tumors. The anti-tumor effect of radiation therapy consists of the direct tumor cell killing, as well as the modulation of tumor microenvironment and the activation of immune response against tumors. Radiation therapy has been shown to promote immunogenic cells death, activate dendritic cells and enhance tumor antigen presentation and anti-tumor T cell activation. Radiation therapy also programs innate immune cells such as macrophages that leads to either radiosensitization or radioresistance, according to different tumors and different radiation regimen studied...
August 2017: Biomedical Journal
https://www.readbyqxmd.com/read/28915659/data-driven-analysis-of-immune-infiltrate-in-a-large-cohort-of-breast-cancer-and-its-association-with-disease-progression-er-activity-and-genomic-complexity
#7
Ruth Dannenfelser, Marianne Nome, Andliena Tahiri, Josie Ursini-Siegel, Hans Kristian Moen Vollan, Vilde D Haakensen, Åslaug Helland, Bjørn Naume, Carlos Caldas, Anne-Lise Børresen-Dale, Vessela N Kristensen, Olga G Troyanskaya
The tumor microenvironment is now widely recognized for its role in tumor progression, treatment response, and clinical outcome. The intratumoral immunological landscape, in particular, has been shown to exert both pro-tumorigenic and anti-tumorigenic effects. Identifying immunologically active or silent tumors may be an important indication for administration of therapy, and detecting early infiltration patterns may uncover factors that contribute to early risk. Thus far, direct detailed studies of the cell composition of tumor infiltration have been limited; with some studies giving approximate quantifications using immunohistochemistry and other small studies obtaining detailed measurements by isolating cells from excised tumors and sorting them using flow cytometry...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915590/combination-of-desi2-and-ip10-gene-therapy-significantly-improves-therapeutic-efficacy-against-murine-carcinoma
#8
Chao Lin, HuaYing Yan, Jun Yang, Lei Li, Mei Tang, Xinyu Zhao, Chunlai Nie, Na Luo, Yuquan Wei, Zhu Yuan
DESI2 (also known as PNAS-4) is a novel pro-apoptotic gene activated during the early response to DNA damage. We previously reported that overexpression of DESI2 induces S phase arrest and apoptosis by activating checkpoint kinases. The present study was designed to test whether combination of DESI2 and IP10 could improve the therapy efficacy in vitro and in vivo. The recombinant plasmid co-expressing DESI2 and IP10 was encapsulated with DOTAP/Cholesterol nanoparticle. Immunocompetent mice bearing CT26 colon carcinoma and LL2 lung cancer were treated with the complex...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912395/-cytotoxic-agents-and-immune-checkpoint-inhibitors
#9
Akihito Kawazoe, Kohei Shitara
It has been reported that favorable influences of cytotoxic agents to anti-tumor immune response included immunogenic cell death and suppression of regulatory T cell and myeloid-derived suppressor cell. Some clinical trials showed that the addition of immune checkpoint inhibitor to standard chemotherapy improved efficacy in patients with non-small-cell lung cancer or malignant melanoma in first-line settings. Phase III trials of the combination of immune checkpoint inhibitor and chemotherapy in several malignancies are ongoing...
September 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28912137/enhanced-cancer-immunotherapy-by-chimeric-antigen-receptor-modified-t-cells-engineered-to-secrete-checkpoint-inhibitors
#10
Pin Wang, Si Li, Natnaree Siriwon, Xiaoyang Zhang, Shuai Yang, Tao Jin, Feng He, Yu Jeong Kim, John Mac, Zhengfei Lu, Sijie Wang, Xiaolu Han
PURPOSE: Despite favorable responses of CAR-engineered T cell therapy in patients with hematologic malignancies, the outcome has been far from satisfactory in the treatment of solid tumors, partially owing to the development of an immunosuppressive tumor microenvironment. To overcome this limitation, we engineered CAR-T cells secreting checkpoint inhibitors (CPIs) targeting PD-1 (CAR.αPD1-T) and evaluated their efficacy in a human lung carcinoma xenograft mouse model. EXPERIMENTAL DESIGN: To evaluate the effector function and expansion capacity of CAR...
September 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28912136/tumor-resection-boosts-therapeutic-efficacy-of-encapsulated-stem-cells-expressing-a-highly-secretable-variant-of-interferon-%C3%AE-in-glioblastomas
#11
Sung Hugh Choi, Daniel W Stuckey, Sara Pignatta, Clemens Reinshagen, Jasneet K Khalsa, Nicolaas C Roozendaal, Jordi Martinez-Quintanilla, Kaoru Tamura, Erhan Keles, Khalid Shah
PURPOSE: Despite tumor resection being the frontline clinical care for glioblastoma (GBM) patients, nearly all preclinical immune therapy models intends to treat established GBM tumor. Characterizing cytoreductive surgery-induced immune-response combined with the administration of immune cytokines has the potential of offering a new treatment paradigm of immune therapy for GBMs.  Experimental design: We developed syngeneic orthotopic mouse GBM models of tumor-resection and characterized the immune response of intact and resected tumors...
September 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28905118/administration-of-low-dose-combination-anti-ctla4-anti-cd137-and-anti-ox40-into-murine-tumor-or-proximal-to-the-tumor-draining-lymph-node-induces-systemic-tumor-regression
#12
Jonathan P O Hebb, Adriane R Mosley, Felipe Vences-Catalán, Narendiran Rajasekaran, Anna Rosén, Peter Ellmark, Dean W Felsher
The delivery of immunomodulators directly into the tumor potentially harnesses the existing antigen, tumor-specific infiltrating lymphocytes, and antigen presenting cells. This can confer specificity and generate a potent systemic anti-tumor immune response with lower doses and less toxicity compared to systemic administration, in effect an in situ vaccine. Here, we test this concept using the novel combination of immunomodulators anti-CTLA4, -CD137, and -OX40. The triple combination administered intratumorally at low doses to one tumor of a dual tumor mouse model had dramatic local and systemic anti-tumor efficacy in lymphoma (A20) and solid tumor (MC38) models, consistent with an abscopal effect...
September 13, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28904432/impact-of-steroids-on-the-inflammatory-response-after-ischemic-acute-kidney-injury-in-rats
#13
J Fontana, A Vogt, A Hohenstein, U Vettermann, E Doroshenko, E Lammer, B A Yard, S Hoeger
Inflammation plays a crucial role in acute kidney injury (AKI). The current study was designed to analyze the influence of prednisolone treatment on the inflammatory reaction during the first 96 h after AKI induction in a rat model. AKI was induced by unilateral clipping of the renal vessels. The treatment group received prednisolone 5 mg/kg s.c. daily. Infiltration rates of macrophages, leukocytes, and T-cells (24, 96 h) as well as plasma concentrations of the inflammatory markers intercellular adhesion molecule, interleukin-1 beta (IL-1β), IL-18, IL-6, and tumor necrosis factor-alpha (0, 6, 24, 96 h) were determined by fluorescence-activated cell sorting (FACS) analysis only...
September 2017: Indian Journal of Nephrology
https://www.readbyqxmd.com/read/28904130/ccr5-dependent-homing-of-t-regulatory-cells-to-the-tumor-microenvironment-contributes-to-skin-squamous-cell-carcinoma-development
#14
Carine Ervolino de Oliveira, Thais Helena Gasparoto, Claudia Ramos Pinheiro, Nádia Ghinelli Amôr, Maria Renata Sales Nogueira, Ramon Kaneno, Gustavo Pompermaier Garlet, Vanessa Soares Lara, João Santana da Silva, Karen Angélica Cavassani, Ana Paula Campanelli
Squamous cell carcinoma (SCC) is one of the most common human cancers worldwide. Recent studies show that regulatory T cells (Tregs) have a critical role in the modulation of an anti- tumor immune response, and consequently the SCC development. Since the accumulation of Tregs at the tumor site is, in part, due to selective recruitment through CCR5 and CCR5-associated chemokines, we investigated the role of CCR5 in the SCC development. Our findings showed that CCR5-deficient mice (CCR5KO) were efficient in controlling papilloma's incidence when compared with wild-type mice...
September 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28904066/pd-1-status-in-cd8-t-cells-associates-with-survival-and-anti-pd-1-therapeutic-outcomes-in-head-and-neck-cancer
#15
Benjamin A Kansy, Fernando Concha-Benavente, Raghvendra M Srivastava, Hyun-Bae Jie, Gulidanna Shayan, Yu Lei, Jessica Moskovitz, Jennifer Moy, Jing Li, Sven Brandau, Stephan Lang, Nicole C Schmitt, Gordon J Freeman, William E Gooding, David A Clump, Robert L Ferris
Improved understanding of expression of immune checkpoint receptors (ICR) on tumor-infiltrating lymphocytes (TIL) may facilitate more effective immunotherapy in head and neck cancer (HNC) patients. A higher frequency of PD-1(+) TIL has been reported in human papillomavirus (HPV)(+) HNC patients, despite the role of PD-1 in T cell exhaustion. This discordance led us to hypothesize that the extent of PD-1 expression more accurately defines T cell function and prognostic impact, since PD-1(high) T cells may be more exhausted than PD-1(low) T cells and may influence clinical outcome and response to anti-PD-1 immunotherapy...
September 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28899967/circulating-cell-free-dna-for-metastatic-cervical-cancer-detection-genotyping-and-monitoring
#16
Zhigang Kang, Sanja Stevanović, Christian S Hinrichs, Liang Cao
PURPOSE: Circulating cell-free (ccf) human papillomavirus (HPV) DNA may serve as a unique tumor marker for HPV-associated malignancies, including cervical cancer. We developed a method to genotype and quantify circulating HPV DNA in patients with HPV16- or HPV18-positive metastatic cervical cancer for potential disease monitoring and treatment-related decision making. PATIENTS AND METHODS: In this retrospective study, HPV ccfDNA was measured in serum samples from 19 metastatic cervical cancer patients by duplex digital droplet (dd) PCR...
September 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28893414/transcriptional-mediated-effects-of-radiation-on-the-expression-of-immune-susceptibility-markers-in-melanoma
#17
Lauryn R Werner, Jasdeep S Kler, Monica M Gressett, Maureen Riegert, Lindsey K Werner, Clinton M Heinze, Joseph G Kern, Mahyar Abbariki, Amy K Erbe, Ravi B Patel, Raghava N Sriramaneni, Paul M Harari, Zachary S Morris
BACKGROUND AND PURPOSE: We recently reported a time-sensitive, cooperative, anti-tumor effect elicited by radiation (RT) and intra-tumoral-immunocytokine injection in vivo. We hypothesized that RT triggers transcriptional-mediated changes in tumor expression of immune susceptibility markers at delayed time points, which may explain these previously observed time-dependent effects. MATERIALS AND METHODS: We examined the time course of changes in expression of immune susceptibility markers following in vitro or in vivo RT in B78 murine melanoma and A375 human melanoma using flow cytometry, immunoblotting, and qPCR...
September 8, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28891906/first-in-human-treatment-with-a-dendritic-cell-targeting-lentiviral-vector-expressing-ny-eso-1-lv305-induces-deep-durable-response-in-refractory-metastatic-synovial-sarcoma-patient
#18
Seth M Pollack, Hailing Lu, Sacha Gnjatic, Neeta Somaiah, Ryan B O'Malley, Robin L Jones, Frank J Hsu, Jan Ter Meulen
Effective induction of antitumor T cells is a pivotal goal of cancer immunotherapy. To this end, lentiviral vectors (LV) are uniquely poised to directly prime CD8 T-cell responses via transduction of dendritic cells in vivo and have shown promise as active cancer therapeutics in preclinical tumor models. However, until now, significant barriers related to production and regulation have prevented their widespread use in the clinic. We developed LV305, a dendritic cell-targeting, integration-deficient, replication incompetent LV from the ZVex platform, encoding the full-length cancer-testis antigen NY-ESO-1...
October 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28888033/modulation-of-%C3%AE-%C3%AE-t-cell-activation-by-neutrophil-elastase
#19
Nadia Yasmín Towstyka, Carolina Maiumi Shiromizu, Irene Keitelman, Florencia Sabbione, Gabriela Verónica Salamone, Jorge Raúl Geffner, Analía Silvina Trevani, Carolina Cristina Jancic
γδ T cells are non-conventional, innate-like T cells, characterized by a restricted TCR repertoire. They participate in protective immunity response against extracellular and intracellular pathogens, tumor surveillance, modulation of innate and adaptive immune responses, tissue healing, epithelial cell maintenance, and regulation of physiological organ function. In this study, we investigated the role of neutrophils during the activation of human blood γδ T cells through CD3 molecules. We found that the up-regulation of CD69 expression, and the production of IFN-γ and TNF-α induced by anti-CD3 antibodies were potentiated by neutrophils...
September 9, 2017: Immunology
https://www.readbyqxmd.com/read/28886381/oncolytic-virotherapy-promotes-intratumoral-t-cell-infiltration-and-improves-anti-pd-1-immunotherapy
#20
Antoni Ribas, Reinhard Dummer, Igor Puzanov, Ari VanderWalde, Robert H I Andtbacka, Olivier Michielin, Anthony J Olszanski, Josep Malvehy, Jonathan Cebon, Eugenio Fernandez, John M Kirkwood, Thomas F Gajewski, Lisa Chen, Kevin S Gorski, Abraham A Anderson, Scott J Diede, Michael E Lassman, Jennifer Gansert, F Stephen Hodi, Georgina V Long
Here we report a phase 1b clinical trial testing the impact of oncolytic virotherapy with talimogene laherparepvec on cytotoxic T cell infiltration and therapeutic efficacy of the anti-PD-1 antibody pembrolizumab. Twenty-one patients with advanced melanoma were treated with talimogene laherparepvec followed by combination therapy with pembrolizumab. Therapy was generally well tolerated, with fatigue, fevers, and chills as the most common adverse events. No dose-limiting toxicities occurred. Confirmed objective response rate was 62%, with a complete response rate of 33% per immune-related response criteria...
September 7, 2017: Cell
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