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Cancer Immunology, Immunotherapy: CII

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https://www.readbyqxmd.com/read/28078357/intralesional-treatment-of-metastatic-melanoma-a-review-of-therapeutic-options
#1
REVIEW
Benjamin Weide, Dario Neri, Giuliano Elia
Intralesional therapy of melanoma patients with locally advanced metastatic disease is attracting increasing interest, not least due to its ability to lead to both direct tumor cell killing and the stimulation of both a local and a systemic immune response. An obvious pre-requisite for this type of approach is the presence of accessible metastases that are amenable to direct injection with the therapeutic agent of interest. Patients who present with these characteristics belong to stages IIIB/C or IV of the disease...
January 11, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28074226/synergistic-effects-of-host-b7-h4-deficiency-and-gemcitabine-treatment-on-tumor-regression-and-anti-tumor-t-cell-immunity-in-a-mouse-model
#2
Joanne Leung, Philippe St-Onge, John Stagg, Woong-Kyung Suh
B7-H4 (B7x/B7S1), a B7 family inhibitor of T cell activity, is expressed in multiple human cancers and correlates with decreased infiltrating lymphocytes and poor prognosis. In murine models, tumor-expressed B7-H4 enhances tumor growth and reduces T cell immunity, and blockade of tumor-B7-H4 rescues T cell activity and lowers tumor burden. This implicates B7-H4 as a target for cancer immunotherapy, yet limits the efficacy of B7-H4 blockade exclusively to patients with B7-H4+ tumors. Given the expression of B7-H4 on host immune cells, we have previously shown that BALB/c mice lacking host B7-H4 have enhanced anti-tumor profiles, yet similar 4T1 tumor growth relative to control...
January 10, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28040849/rejection-versus-escape-the-tumor-mhc-dilemma
#3
REVIEW
Federico Garrido, Francisco Ruiz-Cabello, Natalia Aptsiauri
Most tumor cells derive from MHC-I-positive normal counterparts and remain positive at early stages of tumor development. T lymphocytes can infiltrate tumor tissue, recognize and destroy MHC class I (MHC-I)-positive cancer cells ("permissive" phase I). Later, MHC-I-negative tumor cell variants resistant to T-cell killing emerge. During this process, tumors first acquire a heterogeneous MHC-I expression pattern and finally become uniformly MHC-I-negative. This stage (phase II) represents a "non-permissive" encapsulated structure with tumor nodes surrounded by fibrous tissue containing different elements including leukocytes, macrophages, fibroblasts, etc...
December 31, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28035433/development-of-t-cells-carrying-two-complementary-chimeric-antigen-receptors-against-glypican-3-and-asialoglycoprotein-receptor-1-for-the-treatment-of-hepatocellular-carcinoma
#4
Cheng Chen, Kesang Li, Hua Jiang, Fei Song, Huiping Gao, Xiaorong Pan, Bizhi Shi, Yanyu Bi, Huamao Wang, Hongyang Wang, Zonghai Li
Adoptive immunotherapy leveraging chimeric antigen receptor-modified T (CAR-T) cells holds great promise for the treatment of cancer. However, tumor-associated antigens often have low expression levels in normal tissues, which can cause on-target, off-tumor toxicity. Recently, we reported that GPC3-targeted CAR-T cells could eradicate hepatocellular carcinoma (HCC) xenografts in mice. However, it remains unknown whether on-target, off-tumor toxicity can occur. Therefore, we proposed that dual-targeted CAR-T cells co-expressing glypican-3 (GPC3) and asialoglycoprotein receptor 1 (ASGR1) (a liver tissue-specific protein)-targeted CARs featuring CD3ζ and 28BB (containing both CD28 and 4-1BB signaling domains), respectively, may have reduced on-target, off-tumor toxicity...
December 29, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28011996/the-kinase-inhibitors-r406-and-gs-9973-impair-t-cell-functions-and-macrophage-mediated-anti-tumor-activity-of-rituximab-in-chronic-lymphocytic-leukemia-patients
#5
Ana Colado, María Belén Almejún, Enrique Podaza, Denise Risnik, Carmen Stanganelli, Esteban Enrique Elías, Patricia Dos Santos, Irma Slavutsky, Horacio Fernández Grecco, María Cabrejo, Raimundo Fernando Bezares, Mirta Giordano, Romina Gamberale, Mercedes Borge
Small molecules targeting kinases involved in B cell receptor signaling are showing encouraging clinical activity in chronic lymphocytic leukemia (CLL) patients. Fostamatinib (R406) and entospletinib (GS-9973) are ATP-competitive inhibitors designed to target spleen tyrosine kinase (Syk) that have shown clinical activity with acceptable toxicity in trials with CLL patients. Preclinical studies with these inhibitors in CLL have focused on their effect in patient-derived leukemic B cells. In this work we show that clinically relevant doses of R406 and GS-9973 impaired the activation and proliferation of T cells from CLL patients...
December 23, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28011995/delivery-of-foreign-cytotoxic-t-lymphocyte-epitopes-to-tumor-tissues-for-effective-antitumor-immunotherapy-against-pre-established-solid-tumors-in-mice
#6
Herbert W Kavunja, Shuyao Lang, Suttipun Sungsuwan, Zhaojun Yin, Xuefei Huang
Cytotoxic T lymphocyte (CTL) can have remarkable abilities to kill tumor cells. However, the establishment of successful CTL-based anticancer therapy has met with many challenges. Within tumor cells, there exist subpopulations with low or no expression of the targeted antigen (termed as antigen-loss variants). In addition, tumor cells can downregulate the levels of major histocompatibility complex class I (MHC-I) molecules on cell surface due to immune pressure. As a result, some tumor cells can escape the immune pressure bestowed by CTLs, resulting in treatment failure...
December 23, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28008452/combined-treatment-with-ipilimumab-and-intratumoral-interleukin-2-in-pretreated-patients-with-stage-iv-melanoma-safety-and-efficacy-in-a-phase-ii-study
#7
Benjamin Weide, Alexander Martens, Kilian Wistuba-Hamprecht, Henning Zelba, Ludwig Maier, Hans-Peter Lipp, Bernhard D Klumpp, Daniel Soffel, Thomas K Eigentler, Claus Garbe
Treatment of advanced melanoma patients with ipilimumab results in improved survival. However, only about 20% of treated patients experience long-term benefit. Combining treatment of ipilimumab with other drugs may improve immune activation and potentially enhance clinical efficacy. The aims of the phase II clinical trial reported here were to investigate tolerability and efficacy of a combined immunotherapeutic strategy comprising standard systemic ipilimumab at 3 mg/kg four times at 3-week intervals and intratumorally injected IL-2 at 9 MIU daily twice weekly for four weeks in pretreated melanoma patients with distant metastasis...
December 22, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28005163/intratumoral-th2-predisposition-combines-with-an-increased-th1-functional-phenotype-in-clinical-response-to-intravesical-bcg-in-bladder-cancer
#8
Renate Pichler, Georg Gruenbacher, Zoran Culig, Andrea Brunner, Dietmar Fuchs, Josef Fritz, Hubert Gander, Andrea Rahm, Martin Thurnher
Th1-type immunity is considered to be required for efficient response to BCG in bladder cancer, although Th2 predisposition of BCG responders has recently been reported. The aim was to evaluate the relationship of Th1 and Th2 components in 23 patients undergoing BCG treatment. Peripheral blood, serum and urine samples were prospectively collected at baseline, during and after BCG. Th1 (neopterin, tryptophan, kynurenine, kynurenine-to-tryptophan ratio (KTR), IL-12, IFN-γ, soluble TNF-R75 and IL-2Rα) and Th2 (IL-4, IL-10) biomarkers as well as CD4 expression in T helper (Th), effector and regulatory T cells were determined...
December 22, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27995306/t-cell-receptor-gene-recombinations-in-human-tumor-specimen-exome-files-detection-of-t-cell-receptor-%C3%AE-vdj-recombinations-associates-with-a-favorable-oncologic-outcome-for-bladder-cancer
#9
Mohammad D Samy, Wei Lue Tong, John M Yavorski, Wade J Sexton, George Blanck
Understanding tumor-resident T cells is important for cancer prognosis and treatment options. Conventional, solid tumor specimen exome files can be searched directly for recombined T cell receptor (TcR)-α segments; RNASeq files can include TcR-β VDJ recombinations. To learn whether there are medically relevant uses of exome-based detection of TcR V(D)J recombinations in the tumor microenvironment, we searched cancer genome atlas and Moffitt Cancer Center, tumor specimen exome files for TcR-β, TcR-γ, and TcR-δ recombinations, for bladder and stomach cancer...
December 19, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27987020/bio-hmgb1-from-breast-cancer-contributes-to-m-mdsc-differentiation-from-bone-marrow-progenitor-cells-and-facilitates-conversion-of-monocytes-into-mdsc-like-cells
#10
Zhaoliang Su, Ping Ni, Peng She, Yueqin Liu, Seidu A Richard, Wenlin Xu, Haitao Zhu, Jia Wang
Myeloid-derived suppressor cells (MDSC) constitute the major cell population that regulates immune responses. They are known to accumulate in tumors, chronic inflammatory and autoimmune diseases. Previous data indicate that high mobility group box 1(HMGB1) facilitates MDSC differentiation from bone marrow, suppresses NK cells, CD4(+) and CD8(+) T cells and is involved in cancer development. However, it remains unclear what potential mechanisms of HMGB1 facilitate MDSC differentiation. In the present work, we clearly demonstrate that HMGB1 secreted by cancer cells is N-glycosylated at Asn37, which facilitates monocytic (M)-MDSC differentiation from bone marrow via the p38/NFκB/Erk1/2 pathway and also contributes to conversion of monocytes into MDSC-like cells; HMGB1 blockade by a monoclonal antibody against the HMGB1 B box obviously reduced the accumulation of M-MDSC in tumor-bearing mice, delaying tumor growth and development; additionally, MDSC expansion and HMGB1 up-regulation were also found in breast cancer patients...
December 16, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27942839/immune-modulation-associated-with-vascular-endothelial-growth-factor-vegf-blockade-in-patients-with-glioblastoma
#11
Alissa A Thomas, Jan L Fisher, Thomas H Hampton, Brock C Christensen, Gregory J Tsongalis, Gilbert J Rahme, Chery A Whipple, Sandra E Steel, Melissa C Davis, Arti B Gaur, Lionel D Lewis, Marc S Ernstoff, Camilo E Fadul
BACKGROUND: Vascular endothelial growth factor (VEGF), in addition to being pro-angiogenic, is an immunomodulatory cytokine systemically and in the tumor microenvironment. We previously reported the immunomodulatory effects of radiation and temozolomide (TMZ) in newly diagnosed glioblastoma. This study aimed to assess changes in peripheral blood mononuclear cell (PBMC) populations, plasma cytokines, and growth factor concentrations following treatment with radiation, TMZ, and bevacizumab (BEV)...
December 9, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27933426/characterization-of-the-first-fully-human-anti-tem1-scfv-in-models-of-solid-tumor-imaging-and-immunotoxin-based-therapy
#12
Xiaopeng Yuan, Mingjuan Yang, Xiang Chen, Xuhua Zhang, Shrey Sukhadia, Najia Musolino, Huijing Bao, Tingtao Chen, Chen Xu, Qirui Wang, Stephen Santoro, Daniel Ricklin, Jia Hu, Ruihe Lin, Wei Yang, Zhijun Li, Weijun Qin, Aizhi Zhao
Tumor endothelial marker 1 (TEM1) has been identified as a novel surface marker upregulated on the blood vessels and stroma in many solid tumors. We previously isolated a novel single-chain variable fragment (scFv) 78 against TEM1 from a yeast display scFv library. Here, we evaluated the potential applications of scFv78 as a tool for tumor molecular imaging, immunotoxin-based therapy and nanotherapy. Epitope mapping, three-dimensional structure docking and affinity measurements indicated that scFv78 could bind to both human and murine TEM1, with equivalent affinity, at a well-conserved conformational epitope...
December 8, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27915371/histone-deacetylase-inhibitors-deplete-myeloid-derived-suppressor-cells-induced-by-4t1-mammary-tumors-in-vivo-and-in-vitro
#13
Hai-Fang Wang, Fen Ning, Zong-Cai Liu, Long Wu, Zi-Qian Li, Yi-Fei Qi, Ge Zhang, Hong-Sheng Wang, Shao-Hui Cai, Jun Du
Myeloid-derived suppressor cells (MDSC) have been identified as a population of immature myeloid cells that suppress anti-tumor immunity. MDSC are increased in tumor-bearing hosts; thus, depletion of MDSC may enhance anti-tumor immunity. Histone deacetylase inhibitors (HDACi) are chemical agents that are primarily used against hematologic malignancies. The ability of these agents to modulate anticancer immunity has recently been extensively studied. However, the effect of HDACi on MDSC has remained largely unexplored...
December 3, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27915370/prognostic-significance-of-the-lymphocyte-to-monocyte-ratio-and-the-tumor-infiltrating-lymphocyte-to-tumor-associated-macrophage-ratio-in-patients-with-stage-t3n0m0-esophageal-squamous-cell-carcinoma
#14
Yingming Zhu, Minghuan Li, Cong Bo, Xuemei Liu, Jianbo Zhang, Zhenxiang Li, Fen Zhao, Li Kong, Jinming Yu
PURPOSE: We assessed the prognostic significance of, and the relationship between, the pretreatment lymphocyte-to-monocyte ratio (LMR) and the TILs/tumor-associated macrophages (TAMs) ratio, in patients with esophageal squamous cell carcinoma (ESCC) of pathological stage T3N0M0 (pT3N0M0). METHODS: A total of 220 newly diagnosed ESCC patients of stage pT3N0M0 who had not undergone neoadjuvant therapy were included. Densities of CD8+ TILs, CD4+ TILs, CD45RO+ TILs, and CD68+ TAMs were assessed by immunohistochemical staining of tissue microarray cores from all 220 pT3N0M0 ESCC patients (who underwent radical resection)...
December 3, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27913835/preventive-dna-vaccination-against-cea-expressing-tumors-with-anti-idiotypic-scfv6-c4-dna-in-cea-expressing-transgenic-mice
#15
Priscila M A Denapoli, Bianca F Zanetti, Adara A Dos Santos, Jane Z de Moraes, Sang W Han
Carcinoembryonic antigen (CEA) is expressed during embryonic life and in low level during adult life. Consequently, the CEA is recognized by the immune system as a self-antigen and thus CEA-expressing tumors are tolerated. Previously, we constructed a single chain variable fragment using the 6.C4 (scFv6.C4) hybridoma cell line, which gave rise to antibodies able to recognize CEA when C57/Bl6 mice were immunized. Here, the scFv6.C4 ability to prevent the CEA-expressing tumor growth was assessed in CEA-expressing transgenic mice CEA2682...
December 2, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27896368/targeting-of-the-wt191-138-fragment-to-human-dendritic-cells-improves-leukemia-specific-t-cell-responses-providing-an-alternative-approach-to-wt1-based-vaccination
#16
Nergui Dagvadorj, Anne Deuretzbacher, Daniela Weisenberger, Elke Baumeister, Johannes Trebing, Isabell Lang, Carolin Köchel, Markus Kapp, Kerstin Kapp, Andreas Beilhack, Thomas Hünig, Hermann Einsele, Harald Wajant, Götz Ulrich Grigoleit
Due to its immunogenicity and overexpression concomitant with leukemia progression, Wilms tumor protein 1 (WT1) is of particular interest for immunotherapy of AML relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). So far, WT1-specific T-cell responses have mainly been induced by vaccination with peptides presented by certain HLA alleles. However, this approach is still not widely applicable in clinical practice due to common limitations of HLA restriction. Dendritic cell (DC) vaccines electroporated with mRNA encoding full-length protein have also been tested for generating WT1-derived peptides for presentation to T-cells...
November 28, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27889799/a-polymorphism-in-the-promoter-region-of-pd-l1-serves-as-a-binding-site-for-sp1-and-is-associated-with-pd-l1-overexpression-and-increased-occurrence-of-gastric-cancer
#17
Li-Hua Tao, Xin-Ru Zhou, Fu-Chao Li, Qi Chen, Fan-Yi Meng, Yong Mao, Rui Li, Dong Hua, Hong-Jian Zhang, Wei-Peng Wang, Wei-Chang Chen
PD-L1 is a member of the B7 family co-inhibitory molecules and plays a critical role in tumor immune escape. In this study, we found a polymorphism rs10815225 in the PD-L1 promoter region was significantly associated with the occurrence of gastric cancer. The GG homozygous frequency was higher in the cancer patients than that in the precancerous lesions, which was higher than that in the health controls. This polymorphism locates in the binding-site of Sp1 transcription factor (SP1). The expression level of PD-L1 mRNA in the GG homozygous cancer patients was apparently higher than that in the GC heterozygotes...
November 26, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27889798/selective-effect-of-cytokine-induced-killer-cells-on-survival-of-patients-with-early-stage-melanoma
#18
Hong Li, Lan Huang, Linbo Liu, Ximei Wang, Zhen Zhang, Dongli Yue, Wei He, Kun Fu, Xueli Guo, Jianmin Huang, Xuan Zhao, Yu Zhu, Liping Wang, Wenjie Dong, Yan Yan, Li Xu, Ming Gao, Shuangning Yang, Yi Zhang
Adoptive immunotherapy using cytokine-induced killer (CIK) cells has shown potential antitumor ability against several kinds of cancers, including melanoma. However, little is known about the achievable outcome of CIK cells in melanoma patients at different pathological stages. Here we recruited 55 patients treated with conventional therapy plus CIK cells as the CIK group, and 49 patients treated with conventional therapy alone as the control group. The pathological characteristics were comparable between two groups, with a follow-up period up to 40 months...
November 26, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27888293/cytokine-induced-killer-cells-hunt-individual-cancer-cells-in-droves-in-a-mouse-model
#19
Ji Sung Kim, Yong Guk Kim, Hong Kyung Lee, Eun Jae Park, Boyeong Kim, Jong Soon Kang, Heesoon Lee, Youngsoo Kim, Jin Tae Hong, Sang-Bae Han
Cytotoxicity of cytokine-induced killer (CIK) cells depends mainly on their encounters with target cells, but how many CIK cells are required to kill an individual cancer cell is unknown. Here we used time-lapse imaging to quantify the critical effector cell number required to kill an individual target cell. CIK cells killed MHC-I-negative and MHC-I-positive cancer cells, but natural killer (NK) cells destroyed MHC-I-negative cells only. The average threshold number of CIK cells required to kill an individual cancer cell was 6...
November 25, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27885383/schwann-cells-a-new-player-in-the-tumor-microenvironment
#20
REVIEW
Yuri L Bunimovich, Anton A Keskinov, Galina V Shurin, Michael R Shurin
Cancerous cells must cooperate with the surrounding stroma and non-malignant cells within the microenvironment to support the growth and invasion of the tumor. The nervous system is a component of every organ system of the body, and therefore, is invariably at the front line of the tumor invasion. Due to the complexity of the nervous system physiology, this review separately discusses the contributions of the central and peripheral nervous systems to the tumorigenesis and tumor progression. We further focus the discussion on the evidence that Schwann cells aid in tumor growth and invasion...
November 24, 2016: Cancer Immunology, Immunotherapy: CII
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