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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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...
December 15, 2015: 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
#15
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-)
https://www.readbyqxmd.com/read/26589493/reprogramming-away-from-the-exhausted-t-cell-state
#16
REVIEW
Peter Karagiannis, Shoichi Iriguchi, Shin Kaneko
Induced pluripotent stem cells (iPSCs) describe somatic cells that have been reprogrammed to the pluripotent state from which they can then be differentiated into any cell type of the body. This ability has tremendous implications on a wide number of medical sciences and applications, including cancer treatments. In many cancer patients, tumor infiltrating lymphocytes (TILs) have reached an exhausted state and are unable to exert effector function despite detecting and localizing at the tumor. Although the isolation, ex vivo expansion and transplantation of TILs is effective in a significant group of patients, too many patients do not respond positively to this treatment, in part because the expanded TIL population does not include a sufficient number of cells with the naïve or memory phenotype...
February 2016: Seminars in Immunology
https://www.readbyqxmd.com/read/26451311/characterization-of-t-cell-repertoire-of-blood-tumor-and-ascites-in-ovarian-cancer-patients-using-next-generation-sequencing
#17
Miran Jang, Poh-Yin Yew, Kosei Hasegawa, Yuji Ikeda, Keiichi Fujiwara, Gini F Fleming, Yusuke Nakamura, Jae-Hyun Park
Tumor-infiltrating lymphocytes (TILs) play an important role in regulating the host immune response and are one of key factors in defining tumor microenvironment. Some studies have indicated that T cell infiltration in malignant ascites is associated with clinical outcome, but few studies have performed detailed characterization of T cell diversity or clonality in malignant effusions. We have applied a next generation sequencing method to characterize T cell repertoire of a set of primary cancers, ascites, and blood from 12 ovarian cancer patients and also analyzed the T cell subtype populations in malignant fluids from 3 ovarian cancer patients...
November 2015: Oncoimmunology
https://www.readbyqxmd.com/read/26389673/isolation-of-neoantigen-specific-t-cells-from-tumor-and-peripheral-lymphocytes
#18
Cyrille J Cohen, Jared J Gartner, Miryam Horovitz-Fried, Katerina Shamalov, Kasia Trebska-McGowan, Valery V Bliskovsky, Maria R Parkhurst, Chen Ankri, Todd D Prickett, Jessica S Crystal, Yong F Li, Mona El-Gamil, Steven A Rosenberg, Paul F Robbins
Adoptively transferred tumor-infiltrating T lymphocytes (TILs) that mediate complete regression of metastatic melanoma have been shown to recognize mutated epitopes expressed by autologous tumors. Here, in an attempt to develop a strategy for facilitating the isolation, expansion, and study of mutated antigen-specific T cells, we performed whole-exome sequencing on matched tumor and normal DNA isolated from 8 patients with metastatic melanoma. Candidate mutated epitopes were identified using a peptide-MHC-binding algorithm, and these epitopes were synthesized and used to generate panels of MHC tetramers that were evaluated for binding to tumor digests and cultured TILs used for the treatment of patients...
October 1, 2015: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/26384738/treatment-regimen-surgical-outcome-and-t-cell-differentiation-influence-prognostic-benefit-of-tumor-infiltrating-lymphocytes-in-high-grade-serous-ovarian-cancer
#19
Maartje C A Wouters, Fenne L Komdeur, Hagma H Workel, Harry G Klip, Annechien Plat, Neeltje M Kooi, G Bea A Wisman, Marian J E Mourits, Henriette J G Arts, Maaike H M Oonk, Refika Yigit, Steven de Jong, Cornelis J M Melief, Harry Hollema, Evelien W Duiker, Toos Daemen, Marco de Bruyn, Hans W Nijman
PURPOSE: Tumor-infiltrating lymphocytes (TIL) are associated with a better prognosis in high-grade serous ovarian cancer (HGSC). However, it is largely unknown how this prognostic benefit of TIL relates to current standard treatment of surgical resection and (neo-)adjuvant chemotherapy. To address this outstanding issue, we compared TIL infiltration in a unique cohort of patients with advanced-stage HGSC primarily treated with either surgery or neoadjuvant chemotherapy. EXPERIMENTAL DESIGN: Tissue microarray slides containing samples of 171 patients were analyzed for CD8(+) TIL by IHC...
February 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/26313007/the-identification-of-congeners-and-aliens-by-drosophila-larvae
#20
Francisco Del Pino, Claudia Jara, Luis Pino, María Cristina Medina-Muñoz, Eduardo Alvarez, Raúl Godoy-Herrera
We investigated the role of Drosophila larva olfactory system in identification of congeners and aliens. We discuss the importance of these activities in larva navigation across substrates, and the implications for allocation of space and food among species of similar ecologies. Wild type larvae of cosmopolitan D. melanogaster and endemic D. pavani, which cohabit the same breeding sites, used species-specific volatiles to identify conspecifics and aliens moving toward larvae of their species. D. gaucha larvae, a sibling species of D...
2015: PloS One
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