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tumor infiltrating t lymphocyte

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https://www.readbyqxmd.com/read/29334492/anti-il-10-mediated-enhancement-of-antitumor-efficacy-of-a-dendritic-cell-targeting-mip3%C3%AE-gp100-vaccine-in-the-b16f10-mouse-melanoma-model-is-dependent-on-type-i-interferons
#1
James T Gordy, Kun Luo, Brian Francica, Charles Drake, Richard B Markham
The chemokine MIP3α (CCL20) binds to CCR6 on immature dendritic cells. Vaccines fusing MIP3α to gp100 have been shown to be effective in therapeutically reducing melanoma tumor burden and prolonging survival in a mouse model. Other studies have provided evidence that interleukin-10 (IL-10) neutralizing antibodies (αIL-10) enhance immunologic melanoma therapies by modulating the tolerogenic tumor microenvironment. In the current study, we have utilized the B16F10 syngeneic mouse melanoma model to demonstrate for the first time that a therapy neutralizing IL-10 enhances the antitumor efficacy of a MIP3α-gp100 DNA vaccine, leading to significantly smaller tumors, slower growing tumors, and overall increases in mouse survival...
January 12, 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29331323/regulation-of-inflammatory-factors-by-double-stranded-rna-receptors-in-breast-cancer-cells
#2
Amritha Venkatesh, Harika Nandigam, Maria Muccioli, Manindra Singh, Tiffany Loftus, Deana Lewis, Michelle Pate, Fabian Benencia
Malignant cells are not the only components of a tumor mass since other cells (e.g., fibroblasts, infiltrating leukocytes and endothelial cells) are also part of it. In combination with the extracellular matrix, all these cells constitute the tumor microenvironment. In the last decade the role of the tumor microenvironment in cancer progression has gained increased attention and prompted efforts directed to abrogate its deleterious effects on anti-cancer therapies. The immune system can detect and attack tumor cells, and tumor-infiltrating lymphocytes (particularly CD8 T cells) have been associated with improved survival or better response to therapies in colorectal, melanoma, breast, prostate and ovarian cancer patients among others...
November 22, 2017: Immunobiology
https://www.readbyqxmd.com/read/29330552/dosimetry-prediction-for-clinical-translation-of-64cu-pembrolizumab-immunopet-targeting-human-pd-1-expression
#3
Arutselvan Natarajan, Chirag B Patel, Frezghi Habte, Sanjiv S Gambhir
The immune checkpoint programmed death 1 receptor (PD-1) expressed on some tumor-infiltrating lymphocytes, and its ligand (PD-L1) expressed on tumor cells, enable cancers to evade the immune system. Blocking PD-1 with the monoclonal antibody pembrolizumab is a promising immunotherapy strategy. Thus, noninvasively quantifying the presence of PD-1 expression in the tumor microenvironment prior to initiation of immune checkpoint blockade may identify the patients likely to respond to therapy. We have developed a 64Cu-pembrolizumab radiotracer and evaluated human dosimetry...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29324844/absence-of-myeloid-klf4-reduces-prostate-cancer-growth-with-pro-atherosclerotic-activation-of-tumor-myeloid-cells-and-infiltration-of-cd8-t-cells
#4
David J Barakat, Rahul Suresh, Theresa Barberi, Kenneth J Pienta, Brian W Simons, Alan D Friedman
The microenvironment of prostate cancer often includes abundant tumor-associated macrophages (TAMs), with their acquisition of an M2 phenotype correlating with local aggressiveness and metastasis. Tumor-derived M-CSF contributes to TAM M2 polarization, and M-CSF receptor inhibition slows prostate cancer growth in model systems. As additional cytokines can direct TAM M2 polarization, targeting downstream transcription factors could avoid resistance. Klf4 and C/EBPβ each contribute to monocyte development, and reduced expression of macrophage Klf4 or C/EBPβ favors their adoption of a pro-inflammatory M1 state...
2018: PloS One
https://www.readbyqxmd.com/read/29324830/nano-pulse-stimulation-induces-immunogenic-cell-death-in-human-papillomavirus-transformed-tumors-and-initiates-an-adaptive-immune-response
#5
Joseph G Skeate, Diane M Da Silva, Elena Chavez-Juan, Snjezana Anand, Richard Nuccitelli, W Martin Kast
Nano-Pulse Stimulation (NPS) is a non-thermal pulsed electric field modality that has been shown to have cancer therapeutic effects. Here we applied NPS treatment to the human papillomavirus type 16 (HPV 16)-transformed C3.43 mouse tumor cell model and showed that it is effective at eliminating primary tumors through the induction of immunogenic cell death while subsequently increasing the number of tumor-infiltrating lymphocytes within the tumor microenvironment. In vitro NPS treatment of C3.43 cells resulted in a doubling of activated caspase 3/7 along with the translocation of phosphatidylserine (PS) to the outer leaflet of the plasma membrane, indicating programmed cell death activity...
2018: PloS One
https://www.readbyqxmd.com/read/29324304/injectable-polypeptide-hydrogel-for-dual-delivery-of-antigen-and-tlr3-agonist-to-modulate-dendritic-cells-in%C3%A2-vivo-and-enhance-potent-cytotoxic-t-lymphocyte-response-against-melanoma
#6
Huijuan Song, Pingsheng Huang, Jinfeng Niu, Gaona Shi, Chuangnian Zhang, Deling Kong, Weiwei Wang
Transplantation of immune cells manipulated in vitro to dictate immune responses in the body is promising in cancer immunotherapy. However, this approach suffers from low cell survival after administration, insufficient cell homing to lymph nodes, and off-target. Here we demonstrate an injectable and self-assembled poly(l-valine) hydrogel as the delivery carrier of cargoes including antigen and immunopotentiator for DCs modulation. Our results indicate the vaccine formulation composed of tumor cell lysates (TCL), TLR3 agonist, poly(I:C) and polypeptide hydrogel can robustly recruit, activate and mature DCs in vitro and in vivo by sustained release of TCL and poly(I:C)...
January 3, 2018: Biomaterials
https://www.readbyqxmd.com/read/29320521/cd8-t-cell-infiltration-in-breast-and-colon-cancer-a-histologic-and-statistical-analysis
#7
James Ziai, Houston N Gilbert, Oded Foreman, Jeffrey Eastham-Anderson, Felix Chu, Mahrukh Huseni, Jeong M Kim
The prevalence of cytotoxic tumor infiltrating lymphocytes (TILs) has demonstrated prognostic value in multiple tumor types. In particular, CD8 counts (in combination with CD3 and CD45RO) have been shown to be superior to traditional UICC staging in colon cancer patients and higher total CD8 counts have been associated with better survival in breast cancer patients. However, immune infiltrate heterogeneity can lead to potentially significant misrepresentations of marker prevalence in routine histologic sections...
2018: PloS One
https://www.readbyqxmd.com/read/29312633/the-synergistic-antitumor-effect-of-arsenic-trioxide-combined-with-cytotoxic-t-cells-in-pulmonary-metastasis-model-of-colon-cancer
#8
Lei Wang, Wentao Liang, Na Peng, Xiang Hu, Yingxin Xu, Zhong Liu
Adoptive T cell therapy, including cytotoxic T lymphocytes (CTLs), represents a promising non-toxic anticancer strategy. The effects of this therapy can be impaired by tumor-infiltrated regulatory T cells (Tregs). Autologous murine CTLs acquired using cryopreservation exhibited a cytotoxic effect equivalent to that of conventional CTLs. The killing activity of CTLs was enhanced significantly using arsenic trioxide (ATO), accompanied by reduction in Tregs in vitro. Results using a pulmonary metastasis model of colon cancer indicated that compared with the control group, ATO group, and CTLs group, metastatic node number decreased significantly (p<0...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29308324/neoadjuvant-radiochemotherapy-decreases-the-total-amount-of-tumor-infiltrating-lymphocytes-but-increases-the-number-of-cd8-granzyme-b-grzb-cytotoxic-t-cells-in-rectal-cancer
#9
Armin Jarosch, Ulrich Sommer, Andreas Bogner, Christoph Reißfelder, Jürgen Weitz, Mechthild Krause, Gunnar Folprecht, Gustavo B Baretton, Daniela E Aust
Although neoadjuvant radiochemotherapy (nRCTx) is an established oncological treatment in patients with advanced rectal cancer, little is known about its effects on the tumor microenvironment. Quantity and composition of tumor infiltrating lymphocytes (TILs) are known to influence patients' prognosis but nRCTx-induced modifications are still unclear. We determined the composition of the immune cell infiltrate in rectal cancer after nRCTx and its influence on tumor regression, local recurrence rate and survival...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29308323/two-immune-enhanced-molecular-subtypes-differ-in-inflammation-checkpoint-signaling-and-outcome-of-advanced-head-and-neck-squamous-cell-carcinoma
#10
Bangrong Cao, Qifeng Wang, Huan Zhang, Guiquan Zhu, Jinyi Lang
The immune environment of primary tumor is associated with the clinical response and benefit of immunotherapy. This study aims to investigate the intratumoral immune profile and its clinical relevance in advanced head and neck squamous cell carcinoma (HNSCC). Gene expression profiles of 401 HNSCCs at stage III-IVB from two cohorts (The Cancer Genome Atlas, TCGA, n = 203; the Leipzig Head and Neck Group, LHNG, n = 198) were involved in this analysis. Based on the global immune-related genes, four gene expression subtypes (C1-4) were identified in HNSCCs...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29308315/blockade-of-pd-1-effectively-inhibits-in-vivo-malignant-transformation-of-oral-mucosa
#11
Yichen Chen, Qiusheng Li, Xinye Li, Da Ma, Juan Fang, Liqun Luo, Xiangqi Liu, Xi Wang, Vivian Wai Yan Lui, Juan Xia, Bin Cheng, Zhi Wang
Curbing PD-1 immunosuppressive signaling represents an effective immune awakening or immune-reactivation approach for tumor eradication for many cancers. Yet, the potential involvement of this critical PD-1 immunosuppressive signaling in de novo malignant transformation of epithelial cells to pre-cancerous or cancerous lesions is largely unknown. In this study, we demonstrate that PD-1 signaling is critically involved in de novo malignant transformation of oral mucosa upon carcinogen exposure in vivo. Our findings revealed that 4NQO-treated mice had almost double the numbers of PD-1-positive CD4+ cells and PD-1-positive CD8+ cells in peripheral blood lymphocytes as well as elevated PD-1 expression in tumor infiltrating lymphocytes (when compared to that of control-treated mice), strongly supportive of a general immune-suppression induced by carcinogen challenges in vivo...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29308310/a-novel-immunization-strategy-using-cytokine-chemokines-induces-new-effective-systemic-immune-responses-and-frequent-complete-regressions-of-human-metastatic-melanoma
#12
Fred T Valentine, Frederick M Golomb, Matthew Harris, Daniel F Roses
Immune responses have been elicited by a variety of cancer vaccines, but seldom induce regressions of established cancers in humans. As a novel therapeutic immunization strategy, we tested the hypothesis that multiple cytokines/chemokines secreted early in secondary responses ex-vivo might mimic the secretory environment guiding new immune responses. The early development of immune responses is regulated by multiple cytokines/chemokines acting together, which at physiologic concentrations act locally in concert with antigen to have non-specific effects on adjacent cells, including the maturation of dendritic cells, homing and retention of T cells at the site of antigen, and the differentiation and expansion of T cell clones with appropriate receptors...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29306001/nanoparticulate-vaccine-inhibits-tumor-growth-via-improved-t-cell-recruitment-into-melanoma-and-huher2-breast-cancer
#13
Eva Zupančič, Caterina Curato, Jung-Seok Kim, Eilam Yeini, Ziv Porat, Ana S Viana, Anat Globerson-Levin, Tova Waks, Zelig Eshhar, João N Moreira, Ronit Satchi-Fainaro, Lea Eisenbach, Steffen Jung, Helena F Florindo
Nanoparticulate vaccines are promising tools to overcome cancer immune evasion. However, a deeper understanding on nanoparticle-immune cell interactions and treatments regime are required for optimal efficacy. We provide a comprehensive study of treatment schedules and mode of antigen-association to nanovaccines on the modulation of T cell immunity in vivo, under steady-state and tumor-bearing mice. The coordinated delivery of antigen and two adjuvants (Monophosphoryl lipid A, oligodeoxynucleotide cytosine-phosphate-guanine motifs (CpG)) by nanoparticles was crucial for dendritic cell activation...
January 3, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29305520/soluble-slamf6-receptor-induces-strong-cd8-t-cell-effector-function-and-improves-anti-melanoma-activity-in-vivo
#14
Galit Eisenberg, Roni Engelstein, Anat Geiger, Emma Hajaj, Sharon Merims, Shoshana Frankenburg, Ronny Uzana, Abraham Rutenberg, Arthur Machlenkin, Gabi Frei, Tamar Peretz, Michal Lotem
SLAMF6, a member of the SLAM (signaling lymphocyte activation molecules) family, is a homotypic-binding immune receptor expressed on NK, T, and B lymphocytes. Phosphorylation variance between T-cell subclones prompted us to explore its role in anti-melanoma immunity. Using a 203-amino acid sequence of the human SLAMF6 (seSLAMF6) ectodomain, we found that seSLAMF6 reduced activation-induced cell death and had an anti-apoptotic effect on tumor infiltrating lymphocytes. CD8+ T cells costimulated with seSLAMF6 secreted more interferon gamma and displayed augmented cytolytic activity...
January 5, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29302378/potential-utility-of-fdg-pet-ct-as-a-non-invasive-tool-for-monitoring-local-immune-responses
#15
Seungho Lee, Seohee Choi, Sang Yong Kim, Mi Jin Yun, Hyoung-Il Kim
Purpose: The tumor microenvironment is known to be associated with the metabolic activity of cancer cells and local immune reactions. We hypothesized that glucose metabolism measured by 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) positron emission tomography (PET)-computed tomography (CT) (18F-FDG PET-CT) would be associated with local immune responses evaluated according to the presence of tumor infiltrating lymphocytes (TILs). Materials and Methods: We retrospectively reviewed 56 patients who underwent 18F-FDG PET-CT prior to gastrectomy...
December 2017: Journal of Gastric Cancer
https://www.readbyqxmd.com/read/29301752/t-cell-responses-in-the-microenvironment-of-primary-renal-cell-carcinoma-implications-for-adoptive-cell-therapy
#16
Rikke Andersen, Marie Christine Wulff Westergaard, Julie Westerlin Kjeldsen, Anja Mueller, Natasja Wulff Pedersen, Sine Reker Hadrup, Ozcan Met, Barbara Seliger, Bjarne Kromann-Andersen, Thomas Hasselager, Marco Donia, Inge Marie Svane
In vitro expansion of large numbers of highly potent tumor-reactive T cells appears a prerequisite for effective adoptive cell therapy (ACT) with autologous tumor-infiltrating lymphocytes (TIL) as shown in metastatic melanoma (MM). We therefore sought to determine whether renal cell carcinomas (RCC) are infiltrated with tumor-reactive T cells that could be efficiently employed for adoptive transfer immunotherapy. TILs and autologous tumor cell lines (TCLs) were successfully generated from 22 (92%) and 17 (77%) of 24 consecutive primary RCC specimens and compared to those generated from MM...
January 4, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29301578/notch1-signaling-in-melanoma-cells-promoted-tumor-induced-immunosuppression-via-upregulation-of-tgf-%C3%AE-1
#17
Zike Yang, Yanxia Qi, Nan Lai, Jiahe Zhang, Zehong Chen, Mingyu Liu, Wan Zhang, Rongcheng Luo, Shijun Kang
BACKGROUND: The receptors of Notch family play an important role in controlling the development, differentiation, and function of multiple cell types. The aim of this study is to investigate the role of Notch1 signaling upon immune suppression induced by melanoma cells. METHODS: Melanoma cell line B16 cells were transfected by lentivirus containing mouse Notch1 gene or Notch1 shRNA to generate B16 cell line that highly or lowly expressed Notch1. Notch1 in anti-tumor immune response was comprehensively appraised in murine B16 melanoma tumor model in immunocompetent and immunodeficient mice...
January 4, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29299156/inhibition-of-pi4k-iii%C3%AE-radiosensitizes-in-human-tumor-xenograft-and-immune-competent-syngeneic-murine-tumor-model
#18
Younghee Park, Ji Min Park, Dan Hyo Kim, Jeanny Kwon, In Ah Kim
Phosphatidylinositol (PI) 4-kinase (PI4K) has emerged as a potential target for anti-cancer treatment. We recently reported that simeprevir, an anti-hepatitis C viral (HCV) agent, radiosensitized diverse human cancer cells by inhibiting PI4K IIIα in vitro. In this study, we investigated the radiosensitizing effect of simeprevir in an in vivo tumor xenograft model and the mechanism of its interaction. The immune modulatory effect of PI4K IIIα was evaluated in an immune-competent syngeneic murine tumor model...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29296965/infiltration-of-effector-regulatory-t-cells-predicts-poor-prognosis-of-diffuse-large-b-cell-lymphoma-not-otherwise-specified
#19
Shoko Nakayama, Taiji Yokote, Toshikazu Akioka, Nobuya Hiraoka, Uta Nishiwaki, Takuji Miyoshi, Kazuki Iwaki, Ayami Takayama, Yuki Masuda, Jun Hatooka, Mayumi Fujimoto, Yasuichiro Nishimura, Motomu Tsuji
Regulatory T cells (Tregs) specifically express the transcription factor forkhead box P3 (FOXP3) and contribute to tumor progression. FOXP3-positive cells have been recently proven to be heterogeneous in phenotype and function, including effector Tregs (eTregs), naïve Tregs, and non-Tregs, which harbor no suppressive function. Therefore, it is crucial to investigate the "true Treg (eTreg)" population, rather than the entire FOXP3 population, with regards to their effect on tumor immunity. In particular, in diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), FOXP3-positive cells correlated with a better prognosis...
March 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296775/th17-immune-microenvironment-in-epstein-barr-virus-negative-hodgkin-lymphoma-implications-for-immunotherapy
#20
Amy S Duffield, Maria Libera Ascierto, Robert A Anders, Janis M Taube, Alan K Meeker, Shuming Chen, Tracee L McMiller, Neil A Phillips, Haiying Xu, Aleksandra Ogurtsova, Alan E Berger, Drew M Pardoll, Suzanne L Topalian, Richard F Ambinder
Classical Hodgkin lymphoma (CHL) is a neoplasm characterized by robust inflammatory infiltrates and heightened expression of the immunosuppressive PD-1/PD-L1 pathway. Although anti-PD-1 therapy can be effective in >60% of patients with refractory CHL, improved treatment options are needed for CHLs which are resistant to anti-PD-1 or relapse after this form of immunotherapy. A deeper understanding of immunologic factors in the CHL microenvironment might support the design of more effective treatment combinations based on anti-PD-1...
July 25, 2017: Blood Advances
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