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CD8 cancer tumor melanoma

Frederick J Kohlhapp, Erica J Huelsmann, Andrew T Lacek, Jason M Schenkel, Jevgenijs Lusciks, Joseph R Broucek, Josef W Goldufsky, Tasha Hughes, Janet P Zayas, Hubert Dolubizno, Ryan T Sowell, Regina Kühner, Sarah Burd, John C Kubasiak, Arman Nabatiyan, Sh'Rae Marshall, Praveen K Bommareddy, Shengguo Li, Jenna H Newman, Claude E Monken, Sasha H Shafikhani, Amanda L Marzo, Jose A Guevara-Patino, Ahmed Lasfar, Paul G Thomas, Edmund C Lattime, Howard L Kaufman, Andrew Zloza
In light of increased cancer prevalence and cancer-specific deaths in patients with infections, we investigated whether infections alter anti-tumor immune responses. We report that acute influenza infection of the lung promotes distal melanoma growth in the dermis and leads to accelerated cancer-specific host death. Furthermore, we show that during influenza infection, anti-melanoma CD8(+) T cells are shunted from the tumor to the infection site, where they express high levels of the inhibitory receptor programmed cell death protein 1 (PD-1)...
October 18, 2016: Cell Reports
Hiroyuki Inoue, Jae-Hyun Park, Kazuma Kiyotani, Makda Zewde, Azusa Miyashita, Masatoshi Jinnin, Yukiko Kiniwa, Ryuhei Okuyama, Ryota Tanaka, Yasuhiro Fujisawa, Hiroshi Kato, Akimichi Morita, Jun Asai, Norito Katoh, Kenji Yokota, Masashi Akiyama, Hironobu Ihn, Satoshi Fukushima, Yusuke Nakamura
Immune checkpoint inhibitors blocking the interaction between programmed death-1 (PD-1) and PD-1 ligand-1 (PD-L1) are revolutionizing the cancer immunotherapies with durable clinical responses. Although high expression of PD-L1 in tumor tissues has been implicated to correlate with the better response to the anti-PD-1 therapies, this association has been controversial. In this study, to characterize immune microenvironment in tumors, we examined mRNA levels of immune-related genes and characterized T cell repertoire in the tumors of 13 melanoma patients before and after nivolumab treatment...
2016: Oncoimmunology
Yang Liu, Srilakshmi Pandeswara, Vinh Dao, Álvaro Padrón, Justin M Drerup, Shunhua Lao, Aijie Liu, Vincent Hurez, Tyler J Curiel
mTOR drives tumor growth but also supports T cell function, rendering the applications of mTOR inhibitors complex especially in T cell malignancies. Here we studied the effects of the mTOR inhibitor rapamycin in mouse EL4 T cell lymphoma. Typical pharmacologic rapamycin (1-8 mg/kg) significantly reduced tumor burden via direct suppression of tumor cell proliferation and improved survival in EL4 challenge independent of anti-tumor immunity. Denileukin diftitox (DD)-mediated depletion of regulatory T cells significantly slowed EL4 growth in vivo in a T cell-dependent fashion...
October 13, 2016: Cancer Research
Bo-Ram Lee, Ho Kyung Ko, Ju Hee Ryu, Keum Young Ahn, Young-Ho Lee, Se Jin Oh, Jin Hee Na, Tae Woo Kim, Youngro Byun, Ick Chan Kwon, Kwangmeyung Kim, Jeewon Lee
Efficient delivery of tumor-specific antigens (TSAs) to lymph nodes (LNs) is essential to eliciting robust immune response for cancer immunotherapy but still remains unsolved. Herein, we evaluated the direct LN-targeting performance of four different protein nanoparticles with different size, shape, and origin [Escherichia coli DNA binding protein (DPS), Thermoplasma acidophilum proteasome (PTS), hepatitis B virus capsid (HBVC), and human ferritin heavy chain (hFTN)] in live mice, using an optical fluorescence imaging system...
October 11, 2016: Scientific Reports
Melissa Frick, Pierre Mouchacca, Grégory Verdeil, Yannick Hamon, Cyrille Billaudeau, Michel Buferne, Mathieu Fallet, Nathalie Auphan-Anezin, Anne-Marie Schmitt-Verhulst, Claude Boyer
Cancer-germline genes in both human and mice have been shown to encode antigens susceptible to targeting by cytotoxic CD8 T effector cells (CTL). We analyzed the ability of CTL to kill different tumor cell lines expressing the same cancer-germline gene P1A (Trap1a). We previously demonstrated that CTL expressing a TCR specific for the P1A35-43 peptide associated with H-2L(d) , although able to induce regression of P1A-expressing P815 mastocytoma cells, were much less effective against P1A-expressing melanoma cells...
October 7, 2016: Immunology
Haiyan S Li, Chengwen Liu, Yichuan Xiao, Fuliang Chu, Xiaoxuan Liang, Weiyi Peng, Jianhua Hu, Sattva S Neelapu, Shao-Cong Sun, Patrick Hwu, Stephanie S Watowich
Despite the potent ability of dendritic cells (DCs) to stimulate lymphocyte responses and host immunity, granulocyte-macrophage colony-stimulating factor-derived DCs (GM-DCs) used as antitumor vaccines have demonstrated relatively modest success in cancer immunotherapy. We found that injecting GM-DCs into melanoma tumors in mice, or culturing GM-DCs with melanoma-secreted cytokines or melanoma-conditioned medium, rapidly suppressed DC-intrinsic expression of the gene encoding inhibitor of differentiation 2 (ID2), a transcriptional regulator...
2016: Science Signaling
Piotr Donizy, Przemyslaw Biecek, Agnieszka Halon, Rafal Matkowski
AIM: To develop a multivariable survival model based on histopathological parameters that would provide the best possible estimate of the risk of death in cutaneous melanoma patients. MATERIALS AND METHODS: Breslow thickness and Infiltrating Lymphocytes (BILL(CD8)) is based on two key parameters, namely Breslow thickness and tumor-infiltrating lymphocytes (TILs) shown to be the most important prognostic factors using logistic regression model. The next step was to apply a decision tree method to analyze the impact of the percentage of CD8+ lymphocytes on the risk of cancer death...
September 2016: Anticancer Research
Natalie J Neubert, Charlotte Soneson, David Barras, Petra Baumgaertner, Donata Rimoldi, Mauro Delorenzi, Silvia A Fuertes Marraco, Daniel E Speiser
While T cell-based immunotherapies are steadily improving, there are still many patients who progress, despite T cell-infiltrated tumors. Emerging evidence suggests that T cells themselves may provoke immune escape of cancer cells. Here, we describe a well-controlled co-culture system for studying the dynamic T cell - cancer cell interplay, using human melanoma as a model. We explain starting material, controls, and culture parameters to establish reproducible and comparable cultures with highly heterogeneous tumor cells...
2016: Frontiers in Immunology
Boyan Fang, Andrew McKeon, Shannon R Hinson, Thomas J Kryzer, Sean J Pittock, Allen J Aksamit, Vanda A Lennon
Importance: A novel astrocytic autoantibody has been identified as a biomarker of a relapsing autoimmune meningoencephalomyelitis that is immunotherapy responsive. Seropositivity distinguishes autoimmune glial fibrillary acidic protein (GFAP) meningoencephalomyelitis from disorders commonly considered in the differential diagnosis. Objective: To describe a novel IgG autoantibody found in serum or cerebrospinal fluid that is specific for a cytosolic intermediate filament protein of astrocytes...
September 12, 2016: JAMA Neurology
Aziz Hichami, Akadiri Yessoufou, François Ghiringhelli, Françoise Salvadori, Kabirou Moutairou, Narcisse Zwetyenga, Naim Akhtar Khan
Regulatory T (Treg) cells are important to induce and maintain immunological self-tolerance. Although the progress accomplished in understanding the functional mechanism of Treg cells, intracellular molecules that control the mechanisms of their suppressive capacity are still on investigation. The present study showed that peroxisome proliferator-activated receptor-alpha deficiency impaired the suppressive activity of Treg cells on CD4(+)CD25(-) and CD8(+) T cell proliferation. In Treg cells, PPARα gene deletion also induced a decrease of migratory abilities, and downregulated the expression of chemokine receptors (CCR-4, CCR-8 and CXCR-4) and p27(KIP1) mRNA...
September 6, 2016: Biochimie
Nalin Leelatian, Deon B Doxie, Allison R Greenplate, Bret C Mobley, Jonathan M Lehman, Justine Sinnaeve, Rondi M Kauffmann, Jay A Werkhaven, Akshitkumar M Mistry, Kyle D Weaver, Reid C Thompson, Pierre P Massion, Mary A Hooks, Mark C Kelley, Lola B Chambless, Rebecca A Ihrie, Jonathan M Irish
BACKGROUND: Mass cytometry measures 36 or more markers per cell and is an appealing platform for comprehensive phenotyping of cells in human tissue and tumor biopsies. While tissue disaggregation and fluorescence cytometry protocols were pioneered decades ago, it is not known whether established protocols will be effective for mass cytometry and maintain cancer and stromal cell diversity. METHODS: Tissue preparation techniques were systematically compared for gliomas and melanomas, patient derived xenografts of small cell lung cancer, and tonsil tissue as a control...
September 6, 2016: Cytometry. Part B, Clinical Cytometry
Ana Paula Benaduce, Randall Brenneman, Brett Schrand, Alan Pollack, Eli Gilboa, Adrian Ishkanian
PURPOSE: To report a novel strategy using oligonucleotide aptamers to 4-1BB as an alternate method for costimulation, and show that combinatorial therapy with radiation improves the therapeutic ratio over equivalent monoclonal antibodies. METHODS AND MATERIALS: Subcutaneous 4T1 (mouse mammary carcinoma) tumors were established (approximately 100 mm(3)), and a radiation therapy (RT) dose/fractionation schedule that optimally synergizes with 4-1BB monoclonal antibody (mAb) was identified...
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Blanca Homet Moreno, Jesse M Zaretsky, Angel Garcia-Diaz, Jennifer Tsoi, Giulia Parisi, Lidia Robert, Katrina Meeth, Abibatou Ndoye, Marcus Bosenberg, Ashani T Weeraratna, Thomas G Graeber, Begoña Comin-Anduix, Siwen Hu-Lieskovan, Antoni Ribas
The programmed cell death protein 1 (PD-1) limits effector T-cell functions in peripheral tissues, and its inhibition leads to clinical benefit in different cancers. To better understand how PD-1 blockade therapy modulates the tumor-host interactions, we evaluated three syngeneic murine tumor models, the BRAF(V600E)-driven YUMM1.1 and YUMM2.1 melanomas, and the carcinogen-induced murine colon adenocarcinoma MC38. The YUMM cell lines were established from mice with melanocyte-specific BRAF(V600E) mutation and PTEN loss (BRAF(V600E)/PTEN(-/-))...
October 2016: Cancer Immunology Research
Amalie Kai Bentzen, Andrea Marion Marquard, Rikke Lyngaa, Sunil Kumar Saini, Sofie Ramskov, Marco Donia, Lina Such, Andrew J S Furness, Nicholas McGranahan, Rachel Rosenthal, Per Thor Straten, Zoltan Szallasi, Inge Marie Svane, Charles Swanton, Sergio A Quezada, Søren Nyboe Jakobsen, Aron Charles Eklund, Sine Reker Hadrup
Identification of the peptides recognized by individual T cells is important for understanding and treating immune-related diseases. Current cytometry-based approaches are limited to the simultaneous screening of 10-100 distinct T-cell specificities in one sample. Here we use peptide-major histocompatibility complex (MHC) multimers labeled with individual DNA barcodes to screen >1,000 peptide specificities in a single sample, and detect low-frequency CD8 T cells specific for virus- or cancer-restricted antigens...
October 2016: Nature Biotechnology
Peipei Zhang, James I Andorko, Christopher M Jewell
Biomaterial vaccines offer new capabilities that can be exploited for both infectious disease and cancer. We recently developed a novel vaccine platform based on self-assembly of immune signals into immune polyelectrolyte multilayers (iPEMs). These iPEM vaccines are electrostatically assembled from peptide antigens and nucleic acid-based toll-like receptor agonists (TLRas) that serve as molecular adjuvants. Gold nanoparticles (AuNPs) coated with iPEMs stimulate effector cytokine secretion in vitro and expand antigen-specific T cells in mice...
August 27, 2016: Biotechnology and Bioengineering
Roni Engelstein, Sharon Merims, Galit Eisenberg, Jonathan Cohen, Stephen Frank, Tamar Hamburger, Shoshana Frankenburg, Ilan Ron, Ruth Isacson, Tal Grenader, Hanna Steinberg, Cyrille J Cohen, Tamar Peretz, Michal Lotem
CD8 lymphocytes are mandatory mediators of tumor regression. To enhance their specific antitumor activity, we aimed to improve a melanoma cell-based vaccine by transfecting it with 4-1BB ligand, a costimulatory and immune modulatory molecule. Thirty-four American Joint Committee on Cancer (AJCC) stage IIB-IV patients were vaccinated with a melanoma antigen-rich cell line engineered to express HLA-A2 and 4-1BBL (M20/A2/BBL). Twelve serially recruited patients were monitored for interferon γ expression and CD107a mobilization before and after vaccination...
October 2016: Journal of Immunotherapy
María E Rodriguez-Ruiz, Inmaculada Rodriguez, Saray Garasa, Benigno Barbes, Jose Luis Solorzano, Jose Luis Perez-Gracia, Sara Labiano, Miguel F Sanmamed, Arantza Azpilikueta, Elixabet Bolaños, Alfonso R Sanchez-Paulete, M Angela Aznar, Ana Rouzaut, Kurt A Schalper, Maria Jure-Kunkel, Ignacio Melero
Preclinical and clinical evidence indicate that the proimmune effects of radiotherapy can be synergistically augmented with immunostimulatory mAbs to act both on irradiated tumor lesions and on distant, nonirradiated tumor sites. The combination of radiotherapy with immunostimulatory anti-PD1 and anti-CD137 mAbs was conducive to favorable effects on distant nonirradiated tumor lesions as observed in transplanted MC38 (colorectal cancer), B16OVA (melanoma), and 4T1 (breast cancer) models. The therapeutic activity was crucially performed by CD8 T cells, as found in selective depletion experiments...
October 15, 2016: Cancer Research
Bo Li, Eric Severson, Jean-Christophe Pignon, Haoquan Zhao, Taiwen Li, Jesse Novak, Peng Jiang, Hui Shen, Jon C Aster, Scott Rodig, Sabina Signoretti, Jun S Liu, X Shirley Liu
BACKGROUND: Understanding the interactions between tumor and the host immune system is critical to finding prognostic biomarkers, reducing drug resistance, and developing new therapies. Novel computational methods are needed to estimate tumor-infiltrating immune cells and understand tumor-immune interactions in cancers. RESULTS: We analyze tumor-infiltrating immune cells in over 10,000 RNA-seq samples across 23 cancer types from The Cancer Genome Atlas (TCGA). Our computationally inferred immune infiltrates associate much more strongly with patient clinical features, viral infection status, and cancer genetic alterations than other computational approaches...
2016: Genome Biology
Adil I Daud, Kimberly Loo, Mariela L Pauli, Robert Sanchez-Rodriguez, Priscila Munoz Sandoval, Keyon Taravati, Katy Tsai, Adi Nosrati, Lorenzo Nardo, Michael D Alvarado, Alain P Algazi, Miguel H Pampaloni, Iryna V Lobach, Jimmy Hwang, Robert H Pierce, Iris K Gratz, Matthew F Krummel, Michael D Rosenblum
BACKGROUND: Immune checkpoint blockade is revolutionizing therapy for advanced cancer, but many patients do not respond to treatment. The identification of robust biomarkers that predict clinical response to specific checkpoint inhibitors is critical in order to stratify patients and to rationally select combinations in the context of an expanding array of therapeutic options. METHODS: We performed multiparameter flow cytometry on freshly isolated metastatic melanoma samples from 2 cohorts of 20 patients each prior to treatment and correlated the subsequent clinical response with the tumor immune phenotype...
September 1, 2016: Journal of Clinical Investigation
Spencer Ng, Jiusheng Deng, Raghavan Chinnadurai, Shala Yuan, Andrea Pennati, Jacques Galipeau
The clinical efficacy of immune cytokines used for cancer therapy is hampered by elements of the immunosuppressive tumor microenvironment such as TGFβ. Here we demonstrate that FIST15, a recombinant chimeric protein composed of the T-cell-stimulatory cytokine IL15, the sushi domain of IL15Rα and a TGFβ ligand trap, can overcome immunosuppressive TGFβ to effectively stimulate the proliferation and activation of natural killer (NK) and CD8(+) T cells with potent antitumor properties. FIST15-treated NK and CD8(+) T cells produced more IFNγ and TNFα compared with treatment with IL15 and a commercially available TGFβ receptor-Fc fusion protein (sTβRII) in the presence of TGFβ...
October 1, 2016: Cancer Research
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