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https://www.readbyqxmd.com/read/28226203/characteristic-changes-in-decidual-gene-expression-signature-in-spontaneous-term-parturition
#1
Haidy El-Azzamy, Andrea Balogh, Roberto Romero, Yi Xu, Christopher LaJeunesse, Olesya Plazyo, Zhonghui Xu, Theodore G Price, Zhong Dong, Adi L Tarca, Zoltan Papp, Sonia S Hassan, Tinnakorn Chaiworapongsa, Chong Jai Kim, Nardhy Gomez-Lopez, Nandor Gabor Than
Background: The decidua has been implicated in the "terminal pathway" of human term parturition, which is characterized by the activation of pro-inflammatory pathways in gestational tissues. However, the transcriptomic changes in the decidua leading to terminal pathway activation have not been systematically explored. This study aimed to compare the decidual expression of developmental signaling and inflammation-related genes before and after spontaneous term labor in order to reveal their involvement in this process...
February 22, 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28213366/tumor-infiltrating-and-peripheral-blood-t-cell-immunophenotypes-predict-early-relapse-in-localized-clear-cell-renal-cell-carcinoma
#2
Nicolas A Giraldo, Etienne Becht, Yann Vano, Florent Petitprez, Laetitia Lacroix, Pierre Validire, Rafael Sanchez-Salas, Alexandre Ingels, Stephane Marie Oudard, Audrey Moatti, Bénédicte Buttard, Sarah Bourras, Claire Germain, Xavier Cathelineau, Wolf-Herman Fridman, Catherine Sautes-Fridman
PURPOSE: The efficacy of PD-1 Checkpoint Blockade (ChB) as adjuvant therapy in localized clear cell Renal Cell Carcinoma (ccRCC) is currently unknown. The identification of tumor microenvironment (TME) prognostic biomarkers in this setting may help to define which patients could benefit from ChB and to uncover new therapeutic targets. EXPERIMENTAL DESIGN: We performed multiparametric flow cytometry immunophenotypic analysis of T cells isolated from tumor tissue (TIL), adjacent non-malignant renal tissue (RIL) and peripheral blood (PBL), in a cohort of patients (n=40) with localized ccRCC...
February 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28197366/compensatory-upregulation-of-pd-1-lag-3-and-ctla-4-limits-the-efficacy-of-single-agent-checkpoint-blockade-in-metastatic-ovarian-cancer
#3
Ruea-Yea Huang, Ariel Francois, Aj Robert McGray, Anthony Miliotto, Kunle Odunsi
Tumor-associated or -infiltrating lymphocytes (TALs or TILs) co-express multiple immune inhibitory receptors that contribute to immune suppression in the ovarian tumor microenvironment (TME). Dual blockade of PD-1 along with LAG-3 or CTLA-4 has been shown to synergistically enhance T-cell effector function, resulting in a delay in murine ovarian tumor growth. However, the mechanisms underlying this synergy and the relative contribution of other inhibitory receptors to immune suppression in the ovarian TME are unknown...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28114254/adoptive-cell-therapy-for-metastatic-melanoma
#4
Efrat Merhavi-Shoham, Orit Itzhaki, Gal Markel, Jacob Schachter, Michal J Besser
Adoptive cell therapy (ACT) of tumor-infiltrating lymphocytes (TILs) is a powerful form of immunotherapy by inducing durable complete responses that significantly extend the survival of melanoma patients. Mutation-derived neoantigens were recently identified as key factors for tumor recognition and rejection by TILs. The isolation of T-cell receptor (TCR) genes directed against neoantigens and their retransduction into peripheral T cells may provide a new form of ACT.Genetic modifications of T cells with chimeric antigen receptors (CARs) have demonstrated remarkable clinical results in hematologic malignancies, but are so far less effective in solid tumors...
January 2017: Cancer Journal
https://www.readbyqxmd.com/read/28093446/tumor-infiltrating-merkel-cell-polyomavirus-specific-t-cells-are-diverse-and-associated-with-improved-patient-survival
#5
Natalie J Miller, Candice D Church, Lichun Dong, David Crispin, Matthew P Fitzgibbon, Kristina Lachance, Lichen Jing, Michi Shinohara, Ioannis Gavvovidis, Gerald Willimsky, Martin McIntosh, Thomas Blankenstein, David M Koelle, Paul Nghiem
Tumor-infiltrating CD8(+) T cells are associated with improved survival of patients with Merkel cell carcinoma (MCC), an aggressive skin cancer causally linked to Merkel cell polyomavirus (MCPyV). However, CD8(+) T-cell infiltration is robust in only 4% to 18% of MCC tumors. We characterized the T-cell receptor (TCR) repertoire restricted to one prominent epitope of MCPyV (KLLEIAPNC, "KLL") and assessed whether TCR diversity, tumor infiltration, or T-cell avidity correlated with clinical outcome. HLA-A*02:01/KLL tetramer(+) CD8(+) T cells from MCC patient peripheral blood mononuclear cells (PBMC) and tumor-infiltrating lymphocytes (TIL) were isolated via flow cytometry...
January 16, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/27853635/tumor-infiltrating-tim-3-t-cells-proliferate-avidly-except-when-pd-1-is-co-expressed-evidence-for-intracellular-cross-talk
#6
Jing Li, Gulidanna Shayan, Lyndsay Avery, Hyun-Bae Jie, Neil Gildener-Leapman, Nicole Schmitt, Bin Feng Lu, Lawrence P Kane, Robert L Ferris
Programmed Death 1 (PD-1) and T cell Ig and mucin domain-3 protein (Tim-3) are immune checkpoint receptors highly expressed on tumor infiltrating T lymphocytes (TIL). PD-1 inhibits T cell activation and type-1 T cell responses, while Tim-3 is proposed to mark more extensively exhausted cells, although the mechanisms underlying Tim-3 function are not clear. Trials of anti-PD-1 therapy have identified a large subset of non-responder patients, likely due to expression of alternative checkpoint molecules like Tim-3...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27828929/the-characteristics-of-naive-like-t-cells-in-tumor-infiltrating-lymphocytes-from-human-lung-cancer
#7
Si Yuan Sheng, Yong Gu, Chuan Gang Lu, Ying Ying Tang, Jian Yong Zou, Yu Qing Zhang, Rong Fu Wang, Hai Hong
Adoptive cell therapy using autologous tumor-infiltrating lymphocytes (TILs) or genetically modified lymphocytes from TILs is a new effective approach, but the application of TIL immunotherapy is still limited in many solid tumors. Knowledge of the classification and function of TILs is important to develop personalized immunotherapy with TILs in non-small lung cancer (NSCLC). In this study, we show the characteristics of T-cell subsets in TILs isolated from NSCLC. CD3 CD8 CD45RA T cells outnumbered CD3 CD4 CD45RA T cells in CD45RA TILs, but it was the opposite in CD45RO TILs...
January 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/27827318/isolation-of-t-cell-receptors-specifically-reactive-with-mutated-tumor-associated-antigens-from-tumor-infiltrating-lymphocytes-based-on-cd137-expression
#8
Maria R Parkhurst, Alena Gros, Anna Pasetto, Todd D Prickett, Jessica S Crystal, Paul F Robbins, Steven A Rosenberg
PURPOSE: The adoptive transfer of lymphocytes genetically modified to express tumor reactive T cell receptors (TCRs) can mediate tumor regression. Some tumor infiltrating lymphocytes (TIL) recognize somatic mutations expressed only in the patient's tumors, and evidence suggests that clinically effective TIL target tumor specific neoantigens. Here we attempted to isolate neoantigen reactive TCRs as a prelude to the treatment of patients with autologous T cells genetically modified to express such TCRs...
November 8, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27757315/intratumoral-accumulation-of-podoplanin-expressing-lymph-node-stromal-cells-promote-tumor-growth-through-elimination-of-cd4-tumor-infiltrating-lymphocytes
#9
Aikaterini Hatzioannou, Saba Nayar, Anastasios Gaitanis, Francesca Barone, Constantinos Anagnostopoulos, Panayotis Verginis
The beneficial effects of checkpoint blockade in tumor immunotherapy are limited to patients with increased tumor-infiltrating lymphocytes (TILs). Delineation of the regulatory networks that orchestrate the presence of TILs holds great promise for the design of effective immunotherapies. Podoplanin/gp38 (PDPN)-expressing lymph node stromal cells (LNSCs) are present in tumor stroma; however, their effect in the regulation of TILs remains elusive. Herein we demonstrate that intratumor injection of ex-vivo-isolated PDPN(+) LNSCs into melanoma-bearing mice induces elimination of TILs and promotes tumor growth...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27650547/cd103-intraepithelial-t-cells-in-high-grade-serous-ovarian-cancer-are-phenotypically-diverse-tcr%C3%AE-%C3%AE-cd8%C3%AE-%C3%AE-t-cells-that-can-be-targeted-for-cancer-immunotherapy
#10
Fenne L Komdeur, Maartje C A Wouters, Hagma H Workel, Aline M Tijans, Anouk L J Terwindt, Kim L Brunekreeft, Annechien Plat, Harry G Klip, Florine A Eggink, Ninke Leffers, Wijnand Helfrich, Douwe F Samplonius, Edwin Bremer, G Bea A Wisman, Toos Daemen, Evelien W Duiker, Harry Hollema, Hans W Nijman, Marco de Bruyn
CD103+ tumor-infiltrating lymphocytes (TIL) have been linked to specific epithelial infiltration and a prolonged survival in high-grade serous epithelial ovarian cancer (HGSC). However, whether these cells are induced as part of an ongoing anti-HGSC immune response or represent non-specifically expanded resident or mucosal lymphocytes remains largely unknown. In this study, we first confirmed that CD103+ TIL from HGSC were predominantly localized in the cancer epithelium and were strongly correlated with an improved prognosis...
September 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27612146/assessing-the-impact-of-air-pollution-on-grain-yield-of-winter-wheat-a-case-study-in-the-north-china-plain
#11
Xiuwei Liu, Hongyong Sun, Til Feike, Xiying Zhang, Liwei Shao, Suying Chen
The major wheat production region of China the North China Plain (NCP) is seriously affected by air pollution. In this study, yield of winter wheat (Triticum aestivum L.) was analyzed with respect to the potential impact of air pollution index under conditions of optimal crop management in the NCP from 2001 to 2012. Results showed that air pollution was especially serious at the early phase of winter wheat growth significantly influencing various weather factors. However, no significant correlations were found between final grain yield and the weather factors during the early growth phase...
2016: PloS One
https://www.readbyqxmd.com/read/27526259/-keep-complaining-til-someone-listens-exchanges-of-tacit-healthcare-knowledge-in-online-illness-communities
#12
Drew Foster
This article examines online exchanges of advice and knowledge among patients. It draws a distinction between explicit healthcare knowledge (i.e., facts about symptoms and treatments) and tacit healthcare knowledge (i.e., know-how about navigating the healthcare system). Based on analysis of message board interactions at a prominent online illness community, I find that patients routinely encourage one another to exercise agency strategically in clinical encounters by honing specific interactional skills. I isolate three major techniques that are advocated within the community (affect regulation, information management, and treatment persistence) and frame them as discrete examples of tacit healthcare knowledge...
October 2016: Social Science & Medicine
https://www.readbyqxmd.com/read/27453950/pd-1-blockade-enhances-the-vaccination-induced-immune-response-in-glioma
#13
Joseph P Antonios, Horacio Soto, Richard G Everson, Joey Orpilla, Diana Moughon, Namjo Shin, Shaina Sedighim, William H Yong, Gang Li, Timothy F Cloughesy, Linda M Liau, Robert M Prins
DC vaccination with autologous tumor lysate has demonstrated promising results for the treatment of glioblastoma (GBM) in preclinical and clinical studies. While the vaccine appears capable of inducing T cell infiltration into tumors, the effectiveness of active vaccination in progressively growing tumors is less profound. In parallel, a number of studies have identified negative costimulatory pathways, such as programmed death 1/programmed death ligand 1 (PD-1/PD-L1), as relevant mediators of the intratumoral immune responses...
July 7, 2016: JCI Insight
https://www.readbyqxmd.com/read/27195113/ox40-pd-1-and-ctla-4-are-selectively-expressed-on-tumor-infiltrating-t-cells-in-head-and-neck-cancer
#14
Ryan Montler, R Bryan Bell, Colin Thalhofer, Rom Leidner, Zipei Feng, Bernard A Fox, Allen C Cheng, Tuan G Bui, Christopher Tucker, Helena Hoen, Andrew Weinberg
The tumor microenvironment of squamous cell carcinoma of the head and neck (SCCHN) has been shown to be immune suppressive. Therefore, strategies aimed at overcoming this issue could have a positive therapeutic impact. Hence, we investigated the expression of the known immune-modulatory proteins OX40, programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) in SCCHN on different T-cell subsets of tumor-infiltrating lymphocytes (TIL) to ascertain whether these proteins could potentially be targeted alone or in combination for future clinical trials...
April 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/27163742/metastatic-lung-lesions-as-a-preferred-resection-site-for-immunotherapy-with-tumor-infiltrating-lymphocytes
#15
Ronny Ben-Avi, Orit Itzhaki, David Simansky, Dov Zippel, Gal Markel, Alon Ben Nun, Jacob Schachter, Michal J Besser
Adoptive cell therapy with tumor infiltrating lymphocytes (TIL) yields 50% response rates in metastatic melanoma and shows promising clinical results in other solid tumors. Autologous TIL cultures are isolated from resected tumor tissue, expanded ex vivo to large numbers and reinfused to the preconditioned patient. In this prospective study, we validate the origin of the tumor biopsy and its effect on T-cell function and clinical response. One hundred forty-four patients underwent surgery and 79 patients were treated with TIL adoptive cell therapy...
June 2016: Journal of Immunotherapy
https://www.readbyqxmd.com/read/27070448/targeting-pd-1-and-tim-3-pathways-to-reverse-cd8-t-cell-exhaustion-and-enhance-ex-vivo-t-cell-responses-to-autologous-dendritic-tumor-vaccines
#16
Jingwei Liu, Shurong Zhang, Yuefeng Hu, Zhaomin Yang, Jingpo Li, Xuesong Liu, Lijuan Deng, Yue Wang, Xiaoyan Zhang, Ting Jiang, Xu Lu
The paradoxical coexistence of spontaneous tumor antigen-specific immune response with progressive disease in cancer patients need to dissect the molecular pathways involved in tumor-induced T-cell dysfunction or exhaustion. Programmed cell death 1 (PD-1) has been identified as a marker of exhausted T cells in chronic disease states, and blockade of PD-1-PD-L1 interactions has been shown to partially restore T-cell function. We have found that T-cell immunoglobulin mucin (Tim) 3 is expressed on CD8+ tumor-infiltrating lymphocytes (TILs) isolated from patients with colorectal cancer...
May 2016: Journal of Immunotherapy
https://www.readbyqxmd.com/read/27050669/immune-checkpoint-blockade-to-improve-tumor-infiltrating-lymphocytes-for-adoptive-cell-therapy
#17
Krithika N Kodumudi, Jessica Siegel, Amy M Weber, Ellen Scott, Amod A Sarnaik, Shari Pilon-Thomas
Tumor-infiltrating lymphocytes (TIL) has been associated with improved survival in cancer patients. Within the tumor microenvironment, regulatory cells and expression of co-inhibitory immune checkpoint molecules can lead to the inactivation of TIL. Hence, there is a need to develop strategies that disrupt these negative regulators to achieve robust anti-tumor immune responses. We evaluated the blockade of immune checkpoints and their effect on T cell infiltration and function. We examined the ability of TIL to induce tumor-specific immune responses in vitro and in vivo...
2016: PloS One
https://www.readbyqxmd.com/read/26824221/functional-cloning-of-a-gp100-reactive-t-cell-receptor-from-vitiligo-patient-skin
#18
Jared Klarquist, Jonathan M Eby, Steven W Henning, Mingli Li, Derek A Wainwright, Wiete Westerhof, Rosalie M Luiten, Michael I Nishimura, I Caroline Le Poole
We isolated gp100-reactive T cells from perilesional skin of a patient with progressive vitiligo with superior reactivity toward melanoma cells compared with tumor-infiltrating lymphocytes 1520, a melanoma-derived T-cell line reactive with the same cognate peptide. After dimer enrichment and limited dilution cloning, amplified cells were subjected to reverse transcription and 5' RACE to identify the variable TCRα and TCRβ subunit sequences. The full-length sequence was cloned into a retroviral vector separating both subunits by a P2A slippage sequence and introduced into Jurkat cells and primary T cells...
May 2016: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/26669617/interaction-between-tumour-infiltrating-b-cells-and-t-cells-controls-the-progression-of-hepatocellular-carcinoma
#19
Marta Garnelo, Alex Tan, Zhisheng Her, Joe Yeong, Chun Jye Lim, Jinmiao Chen, Kiat Hon Lim, Achim Weber, Pierce Chow, Alexander Chung, London Lucien Pj Ooi, Han Chong Toh, Mathias Heikenwalder, Irene O L Ng, Alessandra Nardin, Qingfeng Chen, Jean-Pierre Abastado, Valerie Chew
OBJECTIVE: The nature of the tumour-infiltrating leucocytes (TILs) is known to impact clinical outcome in carcinomas, including hepatocellular carcinoma (HCC). However, the role of tumour-infiltrating B cells (TIBs) remains controversial. Here, we investigate the impact of TIBs and their interaction with T cells on HCC patient prognosis. DESIGN: Tissue samples were obtained from 112 patients with HCC from Singapore, Hong Kong and Zurich and analysed using immunohistochemistry and immunofluorescence...
February 2017: Gut
https://www.readbyqxmd.com/read/26590104/intra-tumoral-ifn-%C3%AE-producing-th22-cells-correlate-with-tnm-staging-and-the-worst-outcomes-in-pancreatic-cancer
#20
Elena Niccolai, Antonio Taddei, Federica Ricci, Simona Rolla, Mario Milco D'Elios, Marisa Benagiano, Paolo Bechi, Lapo Bencini, Maria Novella Ringressi, Alessandro Pini, Francesca Castiglione, Daniele Giordano, Maria Antonietta Satolli, Andrea Coratti, Fabio Cianchi, Daniele Bani, Domenico Prisco, Francesco Novelli, Amedeo Amedei
PDAC (pancreatic ductal adenocarcinoma) is the fifth leading cause of cancer-related death. The causes of this cancer remain unknown, but increasing evidence indicates a key role of the host immune response and cytokines in human carcinogenesis. Intra-tumoral IL (interleukin)-22 levels have been shown to be elevated in PDAC patients. However, little is known regarding the expression and clinical relevance of Th22 cells in human PDAC and, furthermore, which TILs (tumour-infiltrating lymphocytes) are the main producers of IL-22 is unknown...
February 2016: Clinical Science (1979-)
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