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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
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
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
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
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
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
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
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
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
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
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-)
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
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
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
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
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
Stephen Mok, Jennifer Tsoi, Richard C Koya, Siwen Hu-Lieskovan, Brian L West, Gideon Bollag, Thomas G Graeber, Antoni Ribas
BACKGROUND: Malignant melanoma is an aggressive tumor type that often develops drug resistance to targeted therapeutics. The production of colony stimulating factor 1 (CSF-1) in tumors recruits myeloid cells such as M2-polarized macrophages and myeloid derived suppressor cells (MDSC), leading to an immune suppressive tumor milieu. METHODS: We used the syngeneic mouse model of BRAF (V600E) -driven melanoma SM1, which secretes CSF-1, to evaluate the ability of the CSF-1 receptor (CSF-1R) inhibitor PLX3397 to improve the antitumor efficacy of the oncogenic BRAF inhibitor vemurafenib...
2015: BMC Cancer
V Baldan, R Griffiths, R E Hawkins, D E Gilham
BACKGROUND: Tumour-infiltrating lymphocyte (TIL) therapy is showing great promise in the treatment of patients with advanced malignant melanoma. However, the translation of TIL therapy to non-melanoma tumours such as renal cell carcinoma has been less successful with a major constraint being the inability to reproducibly generate TILs from primary and metastatic tumour tissue. METHODS: Primary and metastatic renal cell carcinoma biopsies were subjected to differential tumour disaggregation methods and procedures that stimulate the specific expansion of TILs tested to determine which reliably generated TIL maintained antitumour specificity...
April 28, 2015: British Journal of Cancer
Fayçal Djenidi, Julien Adam, Aïcha Goubar, Aurélie Durgeau, Guillaume Meurice, Vincent de Montpréville, Pierre Validire, Benjamin Besse, Fathia Mami-Chouaib
We had previously demonstrated the role of CD103 integrin on lung tumor-infiltrating lymphocyte (TIL) clones in promoting specific TCR-mediated epithelial tumor cell cytotoxicity. However, the contribution of CD103 on intratumoral T cell distribution and functions and the prognosis significance of TIL subpopulations in non-small cell lung carcinoma (NSCLC) have thus far not been systematically addressed. In this study, we show that an enhanced CD103(+) TIL subset correlates with improved early stage NSCLC patient survival and increased intraepithelial lymphocyte infiltration...
April 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
X Wang, I Rivière
Adoptive transfer of tumor-infiltrating lymphocytes (TILs) and genetically engineered T lymphocytes expressing chimeric antigen receptors (CARs) or conventional alpha/beta T-cell receptors (TCRs), collectively termed adoptive cell therapy (ACT), is an emerging novel strategy to treat cancer patients. Application of ACT has been constrained by the ability to isolate and expand functional tumor-reactive T cells. The transition of ACT from a promising experimental regimen to an established standard of care treatment relies largely on the establishment of safe, efficient, robust and cost-effective cell manufacturing protocols...
March 2015: Cancer Gene Therapy
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