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Cancer Immunology, Immunotherapy: CII

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https://www.readbyqxmd.com/read/29150702/high-pdl1-mrna-expression-predicts-better-survival-of-stage-pt1-non-muscle-invasive-bladder-cancer-nmibc-patients
#1
Johannes Breyer, Ralph M Wirtz, Wolfgang Otto, Philipp Erben, Thomas S Worst, Robert Stoehr, Markus Eckstein, Stefan Denzinger, Maximilian Burger, Arndt Hartmann
INTRODUCTION AND OBJECTIVES: Checkpoint inhibition has emerged as new therapeutic option in muscle-invasive bladder cancer. The objective of the present study was to evaluate the prognostic role of PD1 and PDL1 expression in non-muscle-invasive bladder cancer (NMIBC) and establish an objective measuring method using RNA quantification. MATERIALS AND METHODS: We retrospectively analyzed clinical data and formalin-fixed paraffin-embedded tissues (FFPE) of patients with stage pT1 NMIBC who underwent transurethral resection of the bladder...
November 17, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29143114/cancer-vaccine-strategies-translation-from-mice-to-human-clinical-trials
#2
REVIEW
Jay A Berzofsky, Masaki Terabe, Jane B Trepel, Ira Pastan, David F Stroncek, John C Morris, Lauren V Wood
We translated two cancer vaccine strategies from mice into human clinical trials. (1) In preclinical studies on TARP, an antigen expressed in most prostate cancers, we mapped epitopes presented by HLA-A*0201, modified them to increase affinity and immunogenicity in HLA transgenic mice, and induced human T cells that killed human cancer cells ("epitope enhancement"). In a clinical trial, HLA-A2(+) prostate cancer patients with PSA biochemical recurrence (Stage D0) were vaccinated with two peptides either in Montanide-ISA51 or on autologous dendritic cells (DCs)...
November 15, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29127433/targeting-and-suppression-of-her3-positive-breast-cancer-by-t-lymphocytes-expressing-a-heregulin-chimeric-antigen-receptor
#3
Bai-Le Zuo, Bo Yan, Guo-Xu Zheng, Wen-Jin Xi, Xiao Zhang, An-Gang Yang, Lin-Tao Jia
Chimeric antigen receptor-modulated T lymphocytes (CAR-T) have emerged as a powerful tool for arousing anticancer immunity. Endogenous ligands for tumor antigen may outperform single-chain variable fragments to serve as a component of CARs with high cancer recognition efficacy and minimized immunogenicity. As heterodimerization and signaling partners for human epidermal growth factor receptor 2 (HER2), HER3/HER4 has been implicated in tumorigenic signaling and therapeutic resistance of breast cancer. In this study, we engineered T cells with a CAR consisting of the extracellular domain of heregulin-1β (HRG1β) that is a natural ligand for HER3/HER4, and evaluated the specific cytotoxicity of these CAR-T cells in cultured HER3 positive breast cancer cells and xenograft tumors...
November 10, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29124315/the-class-i-iv-hdac-inhibitor-mocetinostat-increases-tumor-antigen-presentation-decreases-immune-suppressive-cell-types-and-augments-checkpoint-inhibitor-therapy
#4
David Briere, Niranjan Sudhakar, David M Woods, Jill Hallin, Lars D Engstrom, Ruth Aranda, Harrah Chiang, Andressa L Sodré, Peter Olson, Jeffrey S Weber, James G Christensen
Checkpoint inhibitor therapy has led to major treatment advances for several cancers including non-small cell lung cancer (NSCLC). Despite this, a significant percentage of patients do not respond or develop resistance. Potential mechanisms of resistance include lack of expression of programmed death ligand 1 (PD-L1), decreased capacity to present tumor antigens, and the presence of an immunosuppressive tumor microenvironment. Mocetinostat is a spectrum-selective inhibitor of class I/IV histone deacetylases (HDACs), a family of proteins implicated in epigenetic silencing of immune regulatory genes in tumor and immune cells...
November 9, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29124314/prophylactic-dna-vaccine-targeting-foxp3-regulatory-t-cells-depletes-myeloid-derived-suppressor-cells-and-improves-anti-melanoma-immune-responses-in-a-murine-model
#5
Afshin Namdar, Reza Mirzaei, Arash Memarnejadian, Roobina Boghosian, Morteza Samadi, Hamid Reza Mirzaei, Hamid Farajifard, Mehdi Zavar, Kayhan Azadmanesh, Shokrollah Elahi, Farshid Noorbakhsh, Abbas Rezaei, Jamshid Hadjati
Regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC) are the two important and interactive immunosuppressive components of the tumor microenvironment that hamper anti-tumor immune responses. Therefore, targeting these two populations together might be beneficial for overcoming immune suppression in the tumor microenvironment. We have recently shown that prophylactic Foxp3 DNA/recombinant protein vaccine (Foxp3 vaccine) promotes immunity against Treg in tumor-free conditions. In the present study, we investigated the immune modulatory effects of a prophylactic regimen of the redesigned Foxp3 vaccine in the B16F10 melanoma model...
November 9, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29116372/tumor-derived-high-mobility-group-box-1-and-thymic-stromal-lymphopoietin-are-involved-in-modulating-dendritic-cells-to-activate-t-regulatory-cells-in-a-mouse-model
#6
Yi Zhang, Zuqiang Liu, Xingxing Hao, Ang Li, Jiying Zhang, Cara D Carey, Louis D Falo, Zhaoyang You
High-mobility group box 1 (HMGB1) is involved in the tumor-associated activation of regulatory T cells (Treg), but the mechanisms remain unknown. In a mouse tumor model, silencing HMGB1 in tumor cells or inhibiting tumor-derived HMGB1 not only dampened the capacity of tumor cells to produce thymic stromal lymphopoietin (TSLP), but also aborted the tumor-associated modulation of Treg-activating DC. Tumor-derived HMGB1 triggered the production of TSLP by tumor cells. Importantly, both tumor-derived HMGB1 and TSLP were necessary for modulating DC to activate Treg in a TSLP receptor (TSLPR)-dependent manner...
November 7, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29094184/braf-peptide-vaccine-facilitates-therapy-of-murine-braf-mutant-melanoma
#7
Qi Liu, Hongda Zhu, Yun Liu, Sara Musetti, Leaf Huang
Approximately, 50% of human melanomas are driven by BRAF mutations, which produce tumors that are highly immunosuppressive and often resistant to vaccine therapy. We introduced lipid-coated calcium phosphate nanoparticles (LCP NPs) as a carrier to efficiently deliver a tumor-specific antigen, the BRAF(V600E) peptide, to drive dendritic cell (DC) maturation and antigen presentation in C57BL6 mice. The BRAF peptide vaccine elicited a robust, antigen-specific cytotoxic T cell response and potent tumor growth inhibition in a murine BRAF-mutant melanoma model...
November 1, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29094183/a-phase-i-vaccination-study-with-dendritic-cells-loaded-with-ny-eso-1-and-%C3%AE-galactosylceramide-induction-of-polyfunctional-t-cells-in-high-risk-melanoma-patients
#8
Olivier Gasser, Katrina J Sharples, Catherine Barrow, Geoffrey M Williams, Evelyn Bauer, Catherine E Wood, Brigitta Mester, Marina Dzhelali, Graham Caygill, Jeremy Jones, Colin M Hayman, Victoria A Hinder, Jerome Macapagal, Monica McCusker, Robert Weinkove, Gavin F Painter, Margaret A Brimble, Michael P Findlay, P Rod Dunbar, Ian F Hermans
Vaccines that elicit targeted tumor antigen-specific T-cell responses have the potential to be used as adjuvant therapy in patients with high risk of relapse. However, the responses induced by vaccines in cancer patients have generally been disappointing. To improve vaccine function, we investigated the possibility of exploiting the immunostimulatory capacity of type 1 Natural killer T (NKT) cells, a cell type enriched in lymphoid tissues that can trigger improved antigen-presenting function in dendritic cells (DCs)...
November 1, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29090321/cross-talk-between-tnf-%C3%AE-and-ifn-%C3%AE-signaling-in-induction-of-b7-h1-expression-in-hepatocellular-carcinoma-cells
#9
Na Li, Jianing Wang, Na Zhang, Mengwei Zhuang, Zhaoyun Zong, Jiahuan Zou, Guosheng Li, Xiaoyan Wang, Huaiyu Zhou, Lining Zhang, Yongyu Shi
Clinical benefit from immunotherapy of B7-H1/PD-1 checkpoint blockade indicates that it is important to understand the regulatory mechanism of B7-H1 expression in cancer cells. As an adaptive response to the endogenous antitumor immunity, B7-H1 expression is up-regulated in HCC cells. B7-H1 expression is induced mainly by IFN-γ released from tumor-infiltrating T cells in HCC. In addition, HCC is a prototype of inflammation-related cancer and TNF-α is a critical component of inflammatory microenvironment of HCC...
October 31, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29085997/cxcl13-expression-is-prognostic-and-predictive-for-postoperative-adjuvant-chemotherapy-benefit-in-patients-with-gastric-cancer
#10
Yichou Wei, Chao Lin, He Li, Zhiying Xu, Jieti Wang, Ruochen Li, Hao Liu, Heng Zhang, Hongyong He, Jiejie Xu
BACKGROUND: Chemokine (C-X-C motif) ligand 13 (CXCL13/BLC/BCA-1) is a cytokine from C-X-C chemokine family, which is selectively chemotactic for B cells. Previous research has demonstrated that high CXCL13 expression is correlated to poor prognosis in various cancers. However, the association between CXCL13 expression and gastric cancer is still unclear. METHODS: Intratumoral CXCL13 expression was evaluated by immunohistochemistry using a semi-quantitative method (modified H-score) in a testing set of 214 and a validation set of 227 randomly selected gastric cancer patients resected in 2008 in one institution...
October 31, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29067496/a-cd3-bispecific-molecule-targeting-p-cadherin-demonstrates-t-cell-mediated-regression-of-established-solid-tumors-in-mice
#11
Timothy S Fisher, Andrea T Hooper, Justin Lucas, Tracey H Clark, Allison K Rohner, Bryan Peano, Mark W Elliott, Konstantinos Tsaparikos, Hui Wang, Jonathan Golas, Maria Gavriil, Nahor Haddish-Berhane, Lioudmila Tchistiakova, Hans-Peter Gerber, Adam R Root, Chad May
Strong evidence exists supporting the important role T cells play in the immune response against tumors. Still, the ability to initiate tumor-specific immune responses remains a challenge. Recent clinical trials suggest that bispecific antibody-mediated retargeted T cells are a promising therapeutic approach to eliminate hematopoietic tumors. However, this approach has not been validated in solid tumors. PF-06671008 is a dual-affinity retargeting (DART(®))-bispecific protein engineered with enhanced pharmacokinetic properties to extend in vivo half-life, and designed to engage and activate endogenous polyclonal T cell populations via the CD3 complex in the presence of solid tumors expressing P-cadherin...
October 24, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29058035/ny-eso-1-and-survivin-specific-t-cell-responses-in-the-peripheral-blood-from-patients-with-glioma
#12
Zhenjiang Liu, Thomas Poiret, Oscar Persson, Qingda Meng, Lalit Rane, Jiri Bartek, Julia Karbach, Hans-Michael Altmannsberger, Christopher Illies, Xiaohua Luo, Inti Harvey-Peredo, Elke Jäger, Ernest Dodoo, Markus Maeurer
The prognosis for patients with glioblastoma is grim. Ex vivo expanded tumor-associated antigen (TAA)-reactive T-cells from patients with glioma may represent a viable source for anticancer-directed cellular therapies. Immunohistochemistry was used to test the survivin (n = 40 samples) and NY-ESO-1 (n = 38 samples) protein expression in tumor specimens. T-cells from peripheral blood were stimulated with TAAs (synthetic peptides) in IL-2 and IL-7, or using a combination of IL-2, IL-15 and IL-21. CD4(+) and CD8(+) T-cells were tested for antigen-specific proliferation by flow cytometry, and IFN-γ production was tested by ELISA...
October 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29058034/fourteenth-meeting-of-the-network-italiano-per-la-bioterapia-dei-tumori-nibit-on-cancer-bio-immunotherapy-siena-italy-october-13-15-2016
#13
Vincenzo Russo, Carla Chiarucci, Maria Fortunata Lofiego, Carolina Fazio, Erica Bertocci, Ornella Cutaia, Gianluca Giacobini, Andrea Lazzeri, Antonello Lamboglia, Maresa Altomonte, Patrizia Tunici, Alessia Covre, Michele Maio
No abstract text is available yet for this article.
October 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29052782/clinical-and-immunologic-evaluation-of-three-metastatic-melanoma-patients-treated-with-autologous-melanoma-reactive-tcr-transduced-t-cells
#14
Tamson Moore, Courtney Regan Wagner, Gina M Scurti, Kelli A Hutchens, Constantine Godellas, Ann Lau Clark, Elizabeth Motunrayo Kolawole, Lance M Hellman, Nishant K Singh, Fernando A Huyke, Siao-Yi Wang, Kelly M Calabrese, Heather D Embree, Rimas Orentas, Keisuke Shirai, Emilia Dellacecca, Elizabeth Garrett-Mayer, Mingli Li, Jonathan M Eby, Patrick J Stiff, Brian D Evavold, Brian M Baker, I Caroline Le Poole, Boro Dropulic, Joseph I Clark, Michael I Nishimura
Malignant melanoma incidence has been increasing for over 30 years, and despite promising new therapies, metastatic disease remains difficult to treat. We describe preliminary results from a Phase I clinical trial (NCT01586403) of adoptive cell therapy in which three patients received autologous CD4(+) and CD8(+) T cells transduced with a lentivirus carrying a tyrosinase-specific TCR and a marker protein, truncated CD34 (CD34t). This unusual MHC Class I-restricted TCR produces functional responses in both CD4(+) and CD8(+) T cells...
October 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29052781/absolute-lymphocyte-counts-at-end-of-induction-correlate-with-distinct-immune-cell-compartments-in-pediatric-b-cell-precursor-acute-lymphoblastic-leukemia
#15
Nina Rolf, Kinga K Smolen, Amina Kariminia, Adam Velenosi, Mario Fidanza, Caron Strahlendorf, Alix E Seif, Gregor S D Reid
Several retrospective studies in children with B cell precursor (BCP) acute lymphoblastic leukemia (ALL) provided clinical evidence that higher absolute lymphocyte counts (ALC) early into treatment significantly correlated with improved relapse-free and overall survival. It still remains unknown, however, whether the predictive role of higher ALCs reflects general bone marrow recovery or a more specific attribute of immune function. To investigate this question, we implemented a prospective observational cohort study in 20 children with BCP ALL on day 29 (D29) of induction chemotherapy and immunophenotyped their lymphoid (T, B and natural killer cells) and myeloid (neutrophils, monocytes, dendritic cells) compartments...
October 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29052780/immunotherapy-for-hepatocellular-carcinoma-patients-is-it-ready-for-prime-time
#16
REVIEW
Joseph M Obeid, Paul R Kunk, Victor M Zaydfudim, Timothy N Bullock, Craig L Slingluff, Osama E Rahma
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the second most common cause of cancer death worldwide. Current treatment options for patients with intermediate and advanced HCC are limited, and there is an unmet need for novel therapeutic approaches. HCC is an attractive target for immunomodulation therapy, since it arises in an inflammatory milieu due to hepatitis B and C infections and cirrhosis. However, a major barrier to the development and success of immunotherapy in patients with HCC is the liver's inherent immunosuppressive function...
October 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29051990/clinicopathologic-implications-of-cd8-foxp3-ratio-and-mir-574-3p-pd-l1-axis-in-spinal-chordoma-patients
#17
Ming-Xiang Zou, Ke-Miao Guo, Guo-Hua Lv, Wei Huang, Jing Li, Xiao-Bin Wang, Yi Jiang, Xiao-Ling She
Currently, little is known about the interactions between microRNAs (miRNAs) and the PD-1/PD-L1 signaling pathway in chordoma, and data discussing the role of the immune milieu in chordoma prognosis are limited. We aimed to analyze the relationship between PD-L1, miR-574-3p, microenvironmental tumor-infiltrating lymphocytes (TILs) and clinicopathological features of spinal chordoma patients. PD-L1 expression and TILs (including Foxp3(+), CD8(+), PD-1(+) and PD-L1(+)) were assessed by immunohistochemistry in tumor specimens of 54 spinal chordoma patients...
October 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29043413/cholecystokinin-receptor-antagonist-alters-pancreatic-cancer-microenvironment-and-increases-efficacy-of-immune-checkpoint-antibody-therapy-in-mice
#18
Jill P Smith, Shangzi Wang, Sandeep Nadella, Sandra A Jablonski, Louis M Weiner
Advanced pancreatic ductal adenocarcinoma (PDAC) has typically been resistant to chemotherapy and immunotherapy; therefore, novel strategies are needed to enhance therapeutic response. Cholecystokinin (CCK) has been shown to stimulate growth of pancreatic cancer. CCK receptors (CCKRs) are present on pancreatic cancer cells, fibroblasts, and lymphocytes. We hypothesized that CCKR blockade would improve response to immune checkpoint antibodies by promoting influx of tumor-infiltrating lymphocytes (TILs) and reducing fibrosis...
October 17, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29026949/a-filamentous-bacteriophage-targeted-to-carcinoembryonic-antigen-induces-tumor-regression-in-mouse-models-of-colorectal-cancer
#19
Paola Murgas, Nicolás Bustamante, Nicole Araya, Sebastián Cruz-Gómez, Eduardo Durán, Diana Gaete, César Oyarce, Ernesto López, Andrés Alonso Herrada, Nicolás Ferreira, Hans Pieringer, Alvaro Lladser
Colorectal cancer is a deadly disease, which is frequently diagnosed at advanced stages, where conventional treatments are no longer effective. Cancer immunotherapy has emerged as a new form to treat different malignancies by turning-on the immune system against tumors. However, tumors are able to evade antitumor immune responses by promoting an immunosuppressive microenvironment. Single-stranded DNA containing M13 bacteriophages are highly immunogenic and can be specifically targeted to the surface of tumor cells to trigger inflammation and infiltration of activated innate immune cells, overcoming tumor-associated immunosuppression and promoting antitumor immunity...
October 12, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29022089/quantification-of-altered-tissue-turnover-in-a-liquid-biopsy-a-proposed-precision-medicine-tool-to-assess-chronic-inflammation-and-desmoplasia-associated-with-a-pro-cancerous-niche-and-response-to-immuno-therapeutic-anti-tumor-modalities
#20
REVIEW
Nicholas Willumsen, Louise B Thomsen, Cecilie L Bager, Christina Jensen, Morten A Karsdal
Immuno-therapy has begun to revolutionize cancer treatment. However, despite the significant progress achieved in regard to the duration of clinical benefits, a substantial number of patients do not respond to these therapies. To improve the outcome of patients receiving immuno-therapy, there is a need for novel biomarkers that can predict and monitor treatment. Tumor microenvironment alterations, more specifically the state of chronic inflammation and desmoplasia (tumor fibrosis), are important factors to consider in this context...
October 11, 2017: Cancer Immunology, Immunotherapy: CII
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