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https://www.readbyqxmd.com/read/29352630/surgical-damage-to-the-lymphatic-system-promotes-tumor-growth-via-impaired-adaptive-immune-response
#1
Yoshiyuki Nakamura, Yasuhiro Fujisawa, Naoko Okiyama, Rei Watanabe, Ryota Tanaka, Yosuke Ishitsuka, Hideaki Tahara, Manabu Fujimoto
BACKGROUND: Both lymph nodes (LNs) and lymphatic channels from primary sites to regional LNs are critical for initiation of adaptive immunity. However, as LNs are common metastatic sites in skin cancers, LN biopsies or dissections are frequently performed. In addition, reconstructive skin flaps after tumor resection may damage lymphatic flow from primary sites to regional LNs. OBJECTIVE: This study was designed to investigate the effect on tumor progression by such surgeries...
December 29, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/29348598/increased-diversity-with-reduced-diversity-evenness-of-tumor-infiltrating-t-cells-for-the-successful-cancer-immunotherapy
#2
Akihiro Hosoi, Kazuyoshi Takeda, Koji Nagaoka, Tamaki Iino, Hirokazu Matsushita, Satoshi Ueha, Shin Aoki, Kouji Matsushima, Masato Kubo, Teppei Morikawa, Kazutaka Kitaura, Ryuji Suzuki, Kazuhiro Kakimi
To facilitate the optimization of cancer immunotherapy lacking immune-related adverse events, we performed TCR repertoire analysis of tumor-infiltrating CD8+ T-cells in B16 melanoma-bearing mice receiving anti-PD-1, anti-CTLA-4, anti-4-1BB, anti-CD4 or a combination of anti-PD-1 and 4-1BB antibodies. Although CD8+ T-cells in the tumor were activated and expanded to a greater or lesser extent by these therapies, tumor growth suppression was achieved only by anti-PD-1, anti-PD-1/4-1BB combined, or by anti-CD4 treatment, but not by anti-CTLA-4 or anti-4-1BB monotherapy...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339377/robust-antitumor-responses-result-from-local-chemotherapy-and-ctla-4-blockade
#3
Charlotte E Ariyan, Mary Sue Brady, Robert H Siegelbaum, Jian Hu, Danielle M Bello, Jamie Green, Charles Fisher, Robert A Lefkowitz, Katherine S Panageas, Melissa Pulitzer, Marissa Vignali, Ryan Emerson, Christopher Tipton, Harlan Robins, Taha Merghoub, Jianda Yuan, Achim Jungbluth, Jorge Blando, Padmanee Sharma, Alexander Y Rudensky, Jedd D Wolchok, James P Allison
Clinical responses to immunotherapy have been associated with augmentation of preexisting immune responses, manifested by heightened inflammation in the tumor microenvironment. However, many tumors have a non-inflamed microenvironment, and response rates to immunotherapy in melanoma have been <50%. We approached this problem by utilizing immunotherapy (CTLA-4 blockade) combined with chemotherapy to induce local inflammation. In murine models of melanoma and prostate cancer, the combination of chemotherapy and CTLA-4 blockade induced a shift in the cellular composition of the tumor microenvironment, with infiltrating CD8+ and CD4+ T cells increasing the CD8/Foxp3 T-cell ratio...
January 16, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29331323/regulation-of-inflammatory-factors-by-double-stranded-rna-receptors-in-breast-cancer-cells
#4
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/29325699/co-delivery-of-tumor-antigen-and-dual-toll-like-receptor-ligands-into-dendritic-cell-by-silicon-microparticle-enables-efficient-immunotherapy-against-melanoma
#5
Motao Zhu, Xilai Ding, Ruifang Zhao, Xuewu Liu, Haifa Shen, Chunmei Cai, Mauro Ferrari, Helen Y Wang, Rong-Fu Wang
Despite the importance and promise of cancer vaccines for broader prevention and treatment of cancer, limited clinical responses are observed, suggesting that key rational designs are required for inducing potent immune responses against cancer. Here we report a mesoporous silicon vector (MSV) as a multi-functional microparticle for formulating an efficient cancer vaccine composed of B16 melanoma derived-tyrosinase related protein 2 (TRP2) peptide and dual toll-like receptor (TLR) agonists. We demonstrated that MSV microparticles protected the peptide from rapid degradation for prolonged antigen presentation to immune cells...
January 8, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
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/29320562/m1-like-macrophages-change-tumor-blood-vessels-and-microenvironment-in-murine-melanoma
#7
Magdalena Jarosz-Biej, Natalia Kamińska, Sybilla Matuszczak, Tomasz Cichoń, Jolanta Pamuła-Piłat, Justyna Czapla, Ryszard Smolarczyk, Daria Skwarzyńska, Klaudia Kulik, Stanisław Szala
Tumor-associated macrophages (TAMs) play a significant role in at least two key processes underlying neoplastic progression: angiogenesis and immune surveillance. TAMs phenotypic changes play important role in tumor vessel abnormalization/ normalization. M2-like TAMs stimulate immunosuppression and formation of defective tumor blood vessels leading to tumor progression. In contrast M1-like TAMs trigger immune response and normalize irregular tumor vascular network which should sensitize cancer cells to chemo- and radiotherapy and lead to tumor growth regression...
2018: PloS One
https://www.readbyqxmd.com/read/29301830/activation-of-4-1bb-on-liver-myeloid-cells-triggers-hepatitis-via-an-interleukin-27-dependent-pathway
#8
Todd Bartkowiak, Ashvin R Jaiswal, Casey R Ager, Renee Chin, Chao-Hsien Chen, Pratha Budhani, Midan Ai, Matthew J Reilley, Manu M Sebastian, David S Hong, Michael A Curran
PURPOSE: Agonist antibodies targeting the T cell co-stimulatory receptor 4-1BB (CD137) are among the most effective immunotherapeutic agents across pre-clinical cancer models. In the clinic, however, development of these agents has been hampered by dose-limiting liver toxicity. Lack of knowledge of the mechanisms underlying this toxicity has limited the potential to separate 4-1BB agonist driven tumor immunity from hepatotoxicity. EXPERIMENTAL DESIGN: The capacity of 4-1BB agonist antibodies to induce liver toxicity was investigated in immunocompetent mice, with or without co-administration of checkpoint blockade, via 1) measurement of serum transaminase levels, 2) imaging of liver immune infiltrates, and 3) qualitative and quantitative assessment of liver myeloid and T cells via flow cytometry...
January 4, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29286146/immune-response-associated-gene-profiling-in-japanese-melanoma-patients-using-multi-omics-analysis
#9
Yasuto Akiyama, Yoshio Kiyohara, Shusuke Yoshikawa, Masaki Otsuka, Ryota Kondou, Chizu Nonomura, Haruo Miyata, Akira Iizuka, Tadashi Ashizawa, Keiichi Ohshima, Kenichi Urakami, Takeshi Nagashima, Masatoshi Kusuhara, Takashi Sugino, Ken Yamaguchi
Project High-tech Omics-based Patient Evaluation (HOPE), including comprehensive whole-exome sequencing (WES) and gene expression profiling (GEP) using freshly resected tumor specimens, has been in progress since its implementation in 2014. Among a total of 1,685 cancer patients, 13 melanoma patients were registered in the HOPE Project and were characterized using multi-omics analyses. Among the 13 melanoma patients, 4 were deceased, and 9 were alive. The mean overall survival (OS) and relapse‑free survival (RFS) times of the melanoma patients were 16...
December 21, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29273790/tnf%C3%AE-blockade-overcomes-resistance-to-anti-pd-1-in-experimental-melanoma
#10
Florie Bertrand, Anne Montfort, Elie Marcheteau, Caroline Imbert, Julia Gilhodes, Thomas Filleron, Philippe Rochaix, Nathalie Andrieu-Abadie, Thierry Levade, Nicolas Meyer, Céline Colacios, Bruno Ségui
Antibodies against programmed cell death-1 (PD-1) have considerably changed the treatment for melanoma. However, many patients do not display therapeutic response or eventually relapse. Moreover, patients treated with anti-PD-1 develop immune-related adverse events that can be cured with anti-tumor necrosis factor α (TNF) antibodies. Whether anti-TNF antibodies affect the anti-cancer immune response remains unknown. Our recent work has highlighted that TNFR1-dependent TNF signalling impairs the accumulation of CD8+ tumor-infiltrating T lymphocytes (CD8+ TILs) in mouse melanoma...
December 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/29224228/newcastle-disease-virus-ndv-co-expressing-il7-and-il15-modified-tumor-cells-as-a-vaccine-for-cancer-immunotherapy
#11
Xiaojing Xu, Qing Sun, Yu Mei, Yonghao Liu, Lixiang Zhao
IL15 and IL7 are two cytokines essential for T cell development and homeostasis. In order to improve the antitumor activity by Newcastle Disease Virus (NDV)-modified tumor vaccine, we generated a recombinant NDV co-expressing IL15 and IL7 (LX/IL(15+7)) by incorporation of a 2A self-processing peptide into IL15 and IL7 using reverse genetics. B16 cells infected with LX/IL(15+7) expressed both IL15 and IL7 stably. The cytotoxicity assay showed that murine melanoma cells modified with LX/IL(15+7) could significantly enhance the antitumor immune response in vitro...
December 10, 2017: Cancer Science
https://www.readbyqxmd.com/read/29217585/patient-hla-class-i-genotype-influences-cancer-response-to-checkpoint-blockade-immunotherapy
#12
Diego Chowell, Luc G T Morris, Claud M Grigg, Jeffrey K Weber, Robert M Samstein, Vladimir Makarov, Fengshen Kuo, Sviatoslav M Kendall, David Requena, Nadeem Riaz, Benjamin Greenbaum, James Carroll, Edward Garon, David M Hyman, Ahmet Zehir, David Solit, Michael Berger, Ruhong Zhou, Naiyer A Rizvi, Timothy A Chan
CD8+ T cell-dependent killing of cancer cells requires efficient presentation of tumor antigens by human leukocyte antigen class I (HLA-I) molecules. However, the extent to which patient-specific HLA-I genotype influences response to anti-PD-1 or anti-CTLA-4 is currently unknown. We determined the HLA-I genotype of 1,535 advanced cancer patients treated with immune checkpoint blockade (ICB). Maximal heterozygosity at HLA-I loci (A, B, and C) improved overall survival after ICB compared to patients who were homozygous for at least one HLA locus...
December 7, 2017: Science
https://www.readbyqxmd.com/read/29190970/genome-wide-identification-of-cancer-testis-genes-and-their-association-with-prognosis-in-a-pan-cancer-analysis
#13
Vandeclecio Lira da Silva, André Faustino Fonseca, Marbella Fonseca, Thayna Emilia da Silva, Ana Carolina Coelho, José Eduardo Kroll, Jorge Estefano Santana de Souza, Beatriz Stransky, Gustavo Antonio de Souza, Sandro José de Souza
Cancer/testis (CT) genes are excellent candidates for cancer immunotherapies because of their restrict expression in normal tissues and the capacity to elicit an immune response when expressed in tumor cells. In this study, we provide a genome-wide screen for CT genes with the identification of 745 putative CT genes. Comparison with a set of known CT genes shows that 201 new CT genes were identified. Integration of gene expression and clinical data led us to identify dozens of CT genes associated with either good or poor prognosis...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29167448/systematic-screening-of-chemokines-to-identify-candidates-to-model-and-create-ectopic-lymph-node-structures-for-cancer-immunotherapy
#14
Yohsuke Yagawa, Mark Robertson-Tessi, Susan L Zhou, Alexander R A Anderson, James J Mulé, Adam W Mailloux
The induction of ectopic lymph node structures (ELNs) holds great promise to augment immunotherapy against multiple cancers including metastatic melanoma, in which ELN formation has been associated with a unique immune-related gene expression signature composed of distinct chemokines. To investigate the therapeutic potential of ELNs induction, preclinical models of ELNs are needed for interrogation of these chemokines. Computational models provide a non-invasive, cost-effective method to investigate leukocyte trafficking in the tumor microenvironment, but parameterizing such models is difficult due to differing assay conditions and contexts among the literature...
November 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29144754/immunogenic-cell-death-amplified-by-co-localized-adjuvant-delivery-for-cancer-immunotherapy
#15
Yuchen Fan, Rui Kuai, Yao Xu, Lukasz J Ochyl, Darrell J Irvine, James J Moon
Despite their potential, conventional whole-cell cancer vaccines prepared by freeze-thawing or irradiation have shown limited therapeutic efficacy in clinical trials. Recent studies have indicated that cancer cells treated with certain chemotherapeutics, such as mitoxantrone, can undergo immunogenic cell death (ICD) and initiate antitumor immune responses. However, it remains unclear how to exploit ICD for cancer immunotherapy. Here, we present a new material-based strategy for converting immunogenically dying tumor cells into a powerful platform for cancer vaccination and demonstrate their therapeutic potential in murine models of melanoma and colon carcinoma...
November 22, 2017: Nano Letters
https://www.readbyqxmd.com/read/29129918/intratumoral-cd40-activation-and-checkpoint-blockade-induces-t-cell-mediated-eradication-of-melanoma-in-the-brain
#16
Manisha Singh, Christina Vianden, Mark J Cantwell, Zhimin Dai, Zhilan Xiao, Meenu Sharma, Hiep Khong, Ashvin R Jaiswal, Faisal Faak, Yared Hailemichael, L M E Janssen, Uddalak Bharadwaj, Michael A Curran, Adi Diab, Roland L Bassett, David J Tweardy, Patrick Hwu, Willem W Overwijk
CD40 agonists bind the CD40 molecule on antigen-presenting cells and activate them to prime tumor-specific CD8+ T cell responses. Here, we study the antitumor activity and mechanism of action of a nonreplicating adenovirus encoding a chimeric, membrane-bound CD40 ligand (ISF35). Intratumoral administration of ISF35 in subcutaneous B16 melanomas generates tumor-specific, CD8+ T cells that express PD-1 and suppress tumor growth. Combination therapy of ISF35 with systemic anti-PD-1 generates greater antitumor activity than each respective monotherapy...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29123966/pd-1-blockade-at-the-time-of-tumor-escape-potentiates-the-immune-mediated-antitumor-effects-of-a-melanoma-targeting-monoclonal-antibody
#17
Laetitia They, Henri-Alexandre Michaud, Ondine Becquart, Virginie Lafont, Bernard Guillot, Florence Boissière-Michot, Marta Jarlier, Caroline Mollevi, Jean-François Eliaou, Nathalie Bonnefoy, Laurent Gros
Tumor antigen-targeting monoclonal antibodies (TA-targeting mAbs) are used as therapeutics in many malignancies and their capacity to mobilize the host immunity puts them at the forefront of anti-cancer immunotherapies. Both innate and adaptive immune cells have been associated with the therapeutic activity of such antibodies, but tumor escape from mAb-induced tumor immune surveillance remains one of the main clinical issues. In this preclinical study, we grafted immunocompetent and immunocompromised mice with the B16F10 mouse melanoma cell line and treated them with the TA99 TA-targeting mAb to analyze the immune mechanisms associated with the tumor response and resistance to TA99 monotherapy...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29123081/resistance-to-cancer-immunotherapy-mediated-by-apoptosis-of-tumor-infiltrating-lymphocytes
#18
Jingjing Zhu, Céline G Powis de Tenbossche, Stefania Cané, Didier Colau, Nicolas van Baren, Christophe Lurquin, Anne-Marie Schmitt-Verhulst, Peter Liljeström, Catherine Uyttenhove, Benoit J Van den Eynde
Despite impressive clinical success, cancer immunotherapy based on immune checkpoint blockade remains ineffective in many patients due to tumoral resistance. Here we use the autochthonous TiRP melanoma model, which recapitulates the tumoral resistance signature observed in human melanomas. TiRP tumors resist immunotherapy based on checkpoint blockade, cancer vaccines or adoptive T-cell therapy. TiRP tumors recruit and activate tumor-specific CD8(+) T cells, but these cells then undergo apoptosis. This does not occur with isogenic transplanted tumors, which are rejected after adoptive T-cell therapy...
November 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/29118259/matrix-binding-checkpoint-immunotherapies-enhance-antitumor-efficacy-and-reduce-adverse-events
#19
Jun Ishihara, Kazuto Fukunaga, Ako Ishihara, Hans M Larsson, Lambert Potin, Peyman Hosseinchi, Gabriele Galliverti, Melody A Swartz, Jeffrey A Hubbell
Immune checkpoint blockade exhibits considerable antitumor activity, but previous studies have reported instances of severe treatment-related adverse events. We sought to explore local immune checkpoint blockade, with an antibody (Ab) form that would be retained intra- or peritumorally, limiting systemic exposure. To accomplish this, we conjugated the checkpoint blockade Abs to an extracellular matrix (ECM)-super-affinity peptide derived from placenta growth factor-2 (PlGF-2123-144). We show enhanced tissue retention and lower Ab concentrations in blood plasma after PlGF-2123-144 conjugation, reducing systemic side effects such as the risk of autoimmune diabetes...
November 8, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29114547/predictive-factors-of-response-to-immunotherapy-a-review-from-the-spanish-melanoma-group-gem
#20
REVIEW
Enrique Espinosa, Ivan Márquez-Rodas, Ainara Soria, Alfonso Berrocal, Jose Luis Manzano, Maria Gonzalez-Cao, Salvador Martin-Algarra
Immunotherapy has become a key element in the treatment of several tumors, such as lung carcinoma and melanoma. Immunotherapy, unlike classical chemotherapy and targeted drugs, may yield long-term survival, even in patients who stop treatment due to toxicity. This fact has generated considerable excitement and a real shift in the paradigm of cancer treatment. However, only a small subset of patients benefit from immunotherapy. Survival curves show that most patients have progression of the disease in the first months after starting immunotherapy, followed by a slower decrease over the first 3 years, until curves reach a plateau...
October 2017: Annals of Translational Medicine
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