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tumor infiltrating lymphocytes

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https://www.readbyqxmd.com/read/28634667/elevated-interleukin-13-receptor-alpha-1-expression-in-tumor-cells-is-associated-with-poor-prognosis-in-patients-with-invasive-breast-cancer
#1
Min Hui Park, Hee Jung Kwon, Jae-Ryong Kim, Byungheon Lee, Soo Jung Lee, Young Kyung Bae
BACKGROUND: Interleukin (IL)-13 is an immunoregulatory, anti-inflammatory cytokine that is produced by numerous immune cells, and plasma membrane receptor for IL-13 (IL-13R) is known to be expressed in various human malignancies and in immune cells. METHODS: The authors evaluated the expression of IL-13R alpha 1 (IL-13Rα1, an IL-13R subtype) by immunohistochemistry in tissue microarrays of 1213 invasive breast cancer (IBC) samples to determine the prognostic value of IL-13Rα1 expression...
June 20, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28634284/co-administration-of-rankl-and-ctla4-antibodies-enhances-lymphocyte-mediated-anti-tumor-immunity-in-mice
#2
Elizabeth Ahern, Heidi Harjunpaa, Deborah Barkauskas, Stacey Allen, Kazuyoshi Takeda, Hideo Yagita, David Wyld, William C Dougall, Michele W L Teng, Mark J Smyth
Purpose: Novel partners for established immune checkpoint inhibitors in the treatment of cancer are needed to address the problems of primary and acquired resistance. The efficacy of combination RANKL and CTLA4 blockade in anti-tumor immunity has been suggested by recent case reports in melanoma. Here we provide a rationale for this combination in mouse models of cancer. <br />Experimental Design: The efficacy and mechanism of a combination of RANKL and CTLA4 blockade was examined by tumor infiltrating lymphocyte analysis, tumor growth and metastasis using a variety of neutralizing antibodies and gene-targeted mice...
June 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28633753/tumor-necrosis-factor-induced-alopecia-alternative-pathology-and-therapy
#3
Jeremy Udkoff, Philip R Cohen
Tumor necrosis factor (TNF) inhibitors are used to treat Crohn disease and psoriasis. Although they are typically well tolerated, adverse effects include the development of alopecia, and paradoxically, psoriatic lesions. We recently described a woman with Crohn disease who developed alopecia and scalp psoriasis during infliximab therapy. After discontinuing infliximab and beginning oral and topical therapies, her alopecia completely resolved. We compared our experience with that of the Craddock et al. who described a woman with Crohn disease and alopecia secondary to adalimumab therapy...
June 15, 2017: Dermatology Online Journal
https://www.readbyqxmd.com/read/28632936/peritumoral-cuffing-by-t-cell-tumor-infiltrating-lymphocytes-distinguishes-hpv-related-oropharyngeal-squamous-cell-carcinoma-from-oral-cavity-squamous-cell-carcinoma
#4
Kate Poropatich, David Hernandez, Joel Fontanarosa, Koshonna Brown, Gayle Woloschak, Ajit Paintal, Kirtee Raparia, Sandeep Samant
BACKGROUND: It is unclear why human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) has improved clinical behavior compared to HPV-negative HNSCC. We sought to better characterize the immune microenvironment of tongue cancers by examining the CD3 and CD8 TIL pattern in HPV-positive and -negative tumors. METHODS: Histologic sections from 40 oral tongue and oropharyngeal cases were analyzed (n= 21 HPV DNA-positive, n= 19 HPV DNA-negative)...
June 20, 2017: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/28631713/-braf-positive-paucicellular-variant-of-anaplastic-carcinoma-in-the-presence-of-tall-cell-variant-papillary-thyroid-cancer
#5
O V Dolzhansky, E M Paltseva, D N Khmelkova, F A Konovalov, I V Kanivets, A V Lavrov, D V Pyankov, S A Korostelev, O A Levendyuk, V M Pominalnaya, D N Fedorov
To paper describes a case of paucicellular anaplastic cancer in the presence of tall cell variant papillary thyroid carcinoma. Microscopic examination showed that the differentiated component of the tumor was composed of papillary structures with tall cells, the height of which exceeded 3-4 times the width. Its anaplastic component consisted of fibrous tissue with occasional spindle-shaped cells and focal lymphocytic infiltration to the extent of 70%. The spindle-shaped cells expressed cytokeratins, β-catenin, p53, and vimentin...
2017: Arkhiv Patologii
https://www.readbyqxmd.com/read/28629762/targeting-the-tumor-and-its-associated-stroma-one-and-one-can-make-three-in-adoptive-t-cell-therapy-of-solid-tumors
#6
Anna Mondino, Gerlanda Vella, Laura Icardi
Adoptive T cell therapy (ACT) has become a promising immunotherapeutic option for cancer patients. The proof for ACT therapeutic efficacy was first obtained with allogenic T cells and then reproduced with T cells isolated from patients' tumor samples (i.e. tumor-infiltrating lymphocytes). It is now clear that specificity of ACT products can be educated by genetically engineering T cells with classical T Cell Receptors (TCR) or chimeric antigen receptors (CAR). To date a poor accessibility of the tumor mass and a hostile microenvironment, influenced by genetic and epigenetic instability, mainly limit ACT therapeutic efficacy in the case of solid tumors...
June 15, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28628234/tumor-targeting-salmonella-typhimurium-a1-r-promotes-tumoricidal-cd8-t-cell-tumor-infiltration-and-arrests-growth-in-a-syngeneic-pancreatic-cancer-orthotopic-mouse-model
#7
Takashi Murakami, Yukihiko Hiroshima, Yong Zhang, Ming Zhao, Tasuku Kiyuna, Ho Kyoung Hwang, Kentaro Miyake, Yuki Homma, Ryutaro Mori, Ryusei Matsuyama, Takashi Chishima, Yasushi Ichikawa, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M Hoffman
The present study determined the effect of tumor-targeting Salmonella typhimurium (S. typhimurium) A1-R on CD8(+) tumor-infiltrating lymphocytes (TILs) in a syngeneic pancreatic cancer orthotopic mouse model. The effect of tumor-targeting Salmonella typhimurium A1-R on CD8(+) TILs was determined on Pan02 murine pancreatic adenocarcinoma cells implanted orthotopically on the pancreatic tail of C57BL/6 mice. Three weeks after orthotopic implantation, mice were randomized into G1: untreated control group (n = 8); and G2: Salmonella typhimurium A1-R treatment group (n = 8, 1 × 10(7) CFU/body, iv, weekly, 3 weeks)...
June 19, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28628092/tissue-resident-memory-features-are-linked-to-the-magnitude-of-cytotoxic-t-cell-responses-in-human-lung-cancer
#8
Anusha-Preethi Ganesan, James Clarke, Oliver Wood, Eva M Garrido-Martin, Serena J Chee, Toby Mellows, Daniela Samaniego-Castruita, Divya Singh, Grégory Seumois, Aiman Alzetani, Edwin Woo, Peter S Friedmann, Emma V King, Gareth J Thomas, Tilman Sanchez-Elsner, Pandurangan Vijayanand, Christian H Ottensmeier
Therapies that boost the anti-tumor responses of cytotoxic T lymphocytes (CTLs) have shown promise; however, clinical responses to the immunotherapeutic agents currently available vary considerably, and the molecular basis of this is unclear. We performed transcriptomic profiling of tumor-infiltrating CTLs from treatment-naive patients with lung cancer to define the molecular features associated with the robustness of anti-tumor immune responses. We observed considerable heterogeneity in the expression of molecules associated with activation of the T cell antigen receptor (TCR) and of immunological-checkpoint molecules such as 4-1BB, PD-1 and TIM-3...
June 19, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28626618/cytoplasmic-expression-of-c-myc-protein-is-associated-with-risk-stratification-of-mantle-cell-lymphoma
#9
Yi Gong, Xi Zhang, Rui Chen, Yan Wei, Zhongmin Zou, Xinghua Chen
AIM: To investigate the association of C-MYC protein expression and risk stratification in mantle cell lymphoma (MCL), and to evaluate the utility of C-MYC protein as a prognostic biomarker in clinical practice. METHODS: We conducted immunohistochemical staining of C-MYC, Programmed cell death ligand 1 (PD-L1), CD8, Ki-67, p53 and SRY (sex determining region Y) -11 (SOX11) to investigate their expression in 64 patients with MCL. The staining results and other clinical data were evaluated for their roles in risk stratification of MCL cases using ANOVA, Chi-square, and Spearman's Rank correlation coefficient analysis...
2017: PeerJ
https://www.readbyqxmd.com/read/28622514/landscape-of-infiltrating-t-cells-in-liver-cancer-revealed-by-single-cell-sequencing
#10
Chunhong Zheng, Liangtao Zheng, Jae-Kwang Yoo, Huahu Guo, Yuanyuan Zhang, Xinyi Guo, Boxi Kang, Ruozhen Hu, Julie Y Huang, Qiming Zhang, Zhouzerui Liu, Minghui Dong, Xueda Hu, Wenjun Ouyang, Jirun Peng, Zemin Zhang
Systematic interrogation of tumor-infiltrating lymphocytes is key to the development of immunotherapies and the prediction of their clinical responses in cancers. Here, we perform deep single-cell RNA sequencing on 5,063 single T cells isolated from peripheral blood, tumor, and adjacent normal tissues from six hepatocellular carcinoma patients. The transcriptional profiles of these individual cells, coupled with assembled T cell receptor (TCR) sequences, enable us to identify 11 T cell subsets based on their molecular and functional properties and delineate their developmental trajectory...
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28621322/reliability-of-tumor-infiltrating-lymphocyte-and-tertiary-lymphoid-structure-assessment-in-human-breast-cancer
#11
Laurence Buisseret, Christine Desmedt, Soizic Garaud, Marco Fornili, Xiaoxiao Wang, Gert Van den Eyden, Alexandre de Wind, Sebastien Duquenne, Anais Boisson, Celine Naveaux, Francoise Rothé, Sandrine Rorive, Christine Decaestecker, Denis Larsimont, Martine Piccart-Gebhart, Elia Biganzoli, Christos Sotiriou, Karen Willard-Gallo
The presence of tumor-infiltrating lymphocytes (TIL), reflecting host immune activity, is frequently correlated with better clinical outcomes, particularly in HER2-positive and triple-negative breast cancer. Recent findings suggest that organization of immune infiltrates in tertiary lymphoid structures also has a beneficial effect on survival. This study investigated inter- and intra-observer variation in TIL assessment using conventional hematoxylin-eosin versus immunohistochemical staining to identify immune cells...
June 16, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28621227/expression-of-epithelial-mesenchymal-transition-driver-brachyury-and-status-of-tumor-infiltrating-cd8-and-foxp3-lymphocytes-in-predicting-treatment-responses-to-neoadjuvant-chemotherapy-of-breast-cancer
#12
Kwan Ho Lee, Eun Young Kim, Yong Lai Park, Sung-Im Do, Seoung Wan Chae, Chan Heun Park
Brachyury has been characterized as a driver of epithelial-mesenchymal transition process which is regarded as an important mechanism of cancer cell invasion and metastatic progression. The status of tumor-infiltrating lymphocytes has been proposed to predict response to neoadjuvant chemotherapy in breast cancer. We investigated the clinical significance and value of tumor-infiltrating lymphocytes and brachyury as biomarkers to predict treatment responses to neoadjuvant chemotherapy in breast cancer. We also examined the correlation of the Neo-Bioscore with tumor-infiltrating lymphocytes and brachyury to indirectly predict long-term outcome...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28614908/adenoviral-production-of-interleukin-2-at-the-tumor-site-removes-the-need-for-systemic-postconditioning-in-adoptive-cell-therapy
#13
Joao Manuel Santos, Riikka Havunen, Mikko Siurala, Víctor Cervera-Carrascon, Siri Tähtinen, Suvi Sorsa, Marjukka Anttila, Pauliina Karell, Anna Kanerva, Akseli Hemminki
Systemic high-dose interleukin-2 (IL-2) postconditioning has long been utilized in boosting the efficacy of T cells in adoptive cell therapy (ACT) of solid tumors. The resulting severe off-target toxicity of these regimens renders local production at the tumor an attractive concept with possible safety gains. We evaluated the efficacy and safety of intratumorally administered IL-2-coding adenoviruses in combination with tumor-infiltrating lymphocyte therapy in syngeneic Syrian hamsters bearing HapT1 pancreatic tumors and with T cell receptor transgenic ACT in B16...
June 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28614802/mitochondrial-dysregulation-and-glycolytic-insufficiency-functionally-impair-cd8-t-cells-infiltrating-human-renal-cell-carcinoma
#14
Peter J Siska, Kathryn E Beckermann, Frank M Mason, Gabriela Andrejeva, Allison R Greenplate, Adam B Sendor, Yun-Chen J Chiang, Armando L Corona, Lelisa F Gemta, Benjamin G Vincent, Richard C Wang, Bumki Kim, Jiyong Hong, Chiu-Lan Chen, Timothy N Bullock, Jonathan M Irish, W Kimryn Rathmell, Jeffrey C Rathmell
Cancer cells can inhibit effector T cells (Teff) through both immunomodulatory receptors and the impact of cancer metabolism on the tumor microenvironment. Indeed, Teff require high rates of glucose metabolism, and consumption of essential nutrients or generation of waste products by tumor cells may impede essential T cell metabolic pathways. Clear cell renal cell carcinoma (ccRCC) is characterized by loss of the tumor suppressor von Hippel-Lindau (VHL) and altered cancer cell metabolism. Here, we assessed how ccRCC influences the metabolism and activation of primary patient ccRCC tumor infiltrating lymphocytes (TIL)...
June 15, 2017: JCI Insight
https://www.readbyqxmd.com/read/28613923/the-era-of-checkpoint-blockade-in-lung-cancer-taking-the-brakes-off-the-immune-system
#15
Edmund K Moon, Corey J Langer, Steven M Albelda
Despite recent advances with targeted kinase inhibitors and better tolerated chemotherapy, the treatment of metastatic non-small cell lung cancer (NSCLC) remains suboptimal. One recent advance that holds great promise is immunotherapy - an approach that enhances a patient's immune system to better recognize and react to abnormal cells. The most successful immunotherapeutic strategy to date uses antibodies to block inhibitory receptors (also called "checkpoints") that are upregulated on the T cells that infiltrate the tumor...
June 14, 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28612127/expression-and-clinical-significance-of-herpes-virus-entry-mediator-hvem-in-breast-cancer
#16
Julia Y S Tsang, Kit-Wing Chan, Yun-Bi Ni, Thazin Hlaing, Jintao Hu, Siu-Ki Chan, Sai-Yin Cheung, Gary M Tse
BACKGROUND: Immune checkpoint blockades are currently actively investigated in invasive breast cancers. Given the complexity of immune regulation, multiple inhibitory molecules within the immune checkpoint framework would be involved in tumor immune escape. Evaluation of the components within the framework is a prerequisite for not only identification of additional treatment targets and optimization of immunotherapeutic strategies but also understanding the prognostic value of these molecules...
June 13, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28611304/immune-profiling-of-nf1-associated-tumors-reveals-histologic-subtype-distinctions-and-heterogeneity-implications-for-immunotherapy
#17
Kellie B Haworth, Michael A Arnold, Christopher R Pierson, Kwangmin Choi, Nicholas D Yeager, Nancy Ratner, Ryan D Roberts, Jonathan L Finlay, Timothy P Cripe
Successful treatment of neurofibromatosis type 1 (NF1)-associated tumors poses a significant clinical challenge. While the primary underlying genetic defect driving RAS signaling is well described, recent evidence suggests immune dysfunction contributes to tumor pathogenesis and malignant transformation. As immunologic characterizations, prognostic and predictive of immunotherapeutic clinical response in other cancers, are not fully described for benign and malignant NF1-related tumors, we sought to define their immunologic profiles...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28611085/ccr6-cc-chemokine-receptor-6-is-essential-for-the-migration-of-detrimental-natural-interleukin-17-producing-%C3%AE-%C3%AE-t-cells-in-stroke
#18
Priyadharshini Arunachalam, Peter Ludewig, Patrick Melich, Thiruma Valavan Arumugam, Christian Gerloff, Immo Prinz, Tim Magnus, Mathias Gelderblom
BACKGROUND AND PURPOSE: Immune-mediated tissue damage after stroke evolves within the first days, and lymphocytes contribute to the secondary injury. Our goal was to identify T-cell subpopulations, which trigger the immune response. METHODS: In a model of experimental stroke, we analyzed the immune phenotype of interleukin-17 (IL-17)-producing γδ T cells and explored the therapeutic potential of neutralizing anti-IL-17 antibodies in combination with mild therapeutic hypothermia...
June 13, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28611044/characterization-of-mk-4166-a-clinical-agonistic-antibody-that-targets-human-gitr-and-inhibits-the-generation-and-suppressive-effects-of-t-regulatory-cells
#19
Selvakumar Sukumar, Douglas C Wilson, Ying Yu, Jerelyn Wong, Saraswathi Naravula, Grigori Ermakov, Romina Riener, Bhagyashree Bhagwat, Antoaneta S Necheva, Jeff Grein, Tatyana Churakova, Ruban Mangadu, Peter Georgiev, Denise Manfra, Elaine M Pinheiro, Venkataraman Sriram, Wendy J Bailey, Danuta Herzyk, Terrill K McClanahan, Aarron Willingham, Amy M Beebe, Svetlana Sadekova
GITR is a T cell co-stimulatory receptor that enhances cellular and humoral immunity. The agonist anti-mouse GITR antibody DTA-1 has demonstrated efficacy in murine models of cancer primarily by attenuation of Treg-mediated immune suppression, but the translatability to human GITR biology has not been fully explored. Here we report the potential utility of MK-4166, a humanized GITR monoclonal antibody selected to bind to an epitope analogous to the DTA-1 epitope, which enhances the proliferation of both naïve and tumor-infiltrating T lymphocytes (TILs)...
June 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28608950/assessment-of-programmed-death-ligand-1-expression-and-tumor-associated-immune-cells-in-pediatric-cancer-tissues
#20
Robbie G Majzner, Jason S Simon, Joseph F Grosso, Daniel Martinez, Bruce R Pawel, Mariarita Santi, Melinda S Merchant, Birgit Geoerger, Imene Hezam, Virginie Marty, Phillippe Vielh, Mads Daugaard, Poul H Sorensen, Crystal L Mackall, John M Maris
BACKGROUND: Programmed death 1 (PD-1) signaling in the tumor microenvironment dampens immune responses to cancer, and blocking this axis induces antitumor effects in several malignancies. Clinical studies of PD-1 blockade are only now being initiated in pediatric patients, and little is known regarding programmed death-ligand 1 (PD-L1) expression in common childhood cancers. The authors characterized PD-L1 expression and tumor-associated immune cells (TAICs) (lymphocytes and macrophages) in common pediatric cancers...
June 13, 2017: Cancer
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