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https://www.readbyqxmd.com/read/28107450/systemic-t-cells-immunosuppression-of-glioma-stem-cell-derived-exosomes-is-mediated-by-monocytic-myeloid-derived-suppressor-cells
#1
Rossana Domenis, Daniela Cesselli, Barbara Toffoletto, Evgenia Bourkoula, Federica Caponnetto, Ivana Manini, Antonio Paolo Beltrami, Tamara Ius, Miran Skrap, Carla Di Loreto, Giorgia Gri
A major contributing factor to glioma development and progression is its ability to evade the immune system. Nano-meter sized vesicles, exosomes, secreted by glioma-stem cells (GSC) can act as mediators of intercellular communication to promote tumor immune escape. Here, we investigated the immunomodulatory properties of GCS-derived exosomes on different peripheral immune cell populations. Healthy donor peripheral blood mononuclear cells (PBMCs) stimulated with anti-CD3, anti-CD28 and IL-2, were treated with GSC-derived exosomes...
2017: PloS One
https://www.readbyqxmd.com/read/28101225/monocytic-myeloid-derived-suppressor-cells-as-a-potent-suppressor-of-tumor-immunity-in-non-small-cell-lung-cancer
#2
Katarzyna Pogoda, Maria Pyszniak, Paweł Rybojad, Jacek Tabarkiewicz
Immunotherapy is a promising therapeutic option for patients with non-small cell lung cancer (NSCLC) who do not qualify for surgery. In patients with advanced NSCLC, systemic immune suppression is frequently observed, therefore, researchers are investigating the tumor microenvironment for less invasive and more effective methods of treating lung cancer. Monocytic myeloid-derived suppressor cells (Mo-MDSCs) are potent suppressors of tumor immunity; therefore, this population may significantly impede the application of immunotherapy to treat cancer...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28099196/use-of-engineered-exosomes-expressing-hla-and-costimulatory-molecules-to-generate-antigen-specific-cd8-t-cells-for-adoptive-cell-therapy
#3
Sueon Kim, Hyun-Jung Sohn, Hyun-Joo Lee, Dae-Hee Sohn, Seung-Joo Hyun, Hyun-Il Cho, Tai-Gyu Kim
Dendritic cell-derived exosomes (DEX) comprise an efficient stimulator of T cells. However, the production of sufficient DEX remains a barrier to their broad applicability in immunotherapeutic approaches. In previous studies, genetically engineered K562 have been used to generate artificial antigen presenting cells (AAPC). Here, we isolated exosomes from K562 cells (referred to as CoEX-A2s) engineered to express human leukocyte antigen (HLA)-A2 and costimulatory molecules such as CD80, CD83, and 41BBL. CoEX-A2s were capable of stimulating antigen-specific CD8 T cells both directly and indirectly via CoEX-A2 cross-dressed cells...
January 17, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28099147/ctla-4-positive-breast-cancer-cells-suppress-dendritic-cells-maturation-and-function
#4
Xi Chen, Qianqian Shao, Shengnan Hao, Zhonghua Zhao, Yang Wang, Xiaofan Guo, Ying He, Wenjuan Gao, Haiting Mao
Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), a potent immunoregulatory molecule, can down-regulate T-cell activation and inhibit anti-tumor immune response. This study showed that LPS-stimulated human dendritic cells (DCs) decreased the expression of HLA-DR, CD83 and costimulatory molecules (CD40, CD80 and CD86) following coculturing with CTLA-4+ breast cancer cells. Moreover, the suppressed DCs further inhibited proliferation of allogeneic CD4+/CD8+ T-cells, differentiation of Th1 and function of cytotoxic lymphocytes (CTLs)...
January 13, 2017: Oncotarget
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/28088513/an-immunogram-for-the-cancer-immunity-cycle-towards-personalized-immunotherapy-of-lung-cancer
#6
Takahiro Karasaki, Kazuhiro Nagayama, Hideki Kuwano, Jun-Ichi Nitadori, Masaaki Sato, Masaki Anraku, Akihiro Hosoi, Hirokazu Matsushita, Yasuyuki Morishita, Kosuke Kashiwabara, Masaki Takazawa, Osamu Ohara, Kazuhiro Kakimi, Jun Nakajima
INTRODUCTION: The interaction of immune cells and cancer cells shapes the immunosuppressive tumor microenvironment. For successful cancer immunotherapy, comprehensive knowledge of anti-tumor immunity as a dynamic spacio-temporal process is required for each individual patient. To this end, we developed an immunogram for the cancer-immunity cycle using next-generation sequencing. METHODS: Whole-exome sequencing and RNA-Seq was performed in 20 non-small cell lung cancer patients (12 adenocarcinoma, 7 squamous cell carcinoma, and 1 large cell neuroendocrine carcinoma)...
January 11, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28078984/rasburicase-induced-methemoglobinemia-in-a-patient-with-glucose-6-phosphate-dehydrogenase-deficiency
#7
Maliha Khan, Shilpa Paul, Saad Farooq, Thein Hlaing Oo, Priya Ramshesh, Nitin Jain
BACKGROUND: Rasburicase is commonly used in patients with hematologic malignancies for tumor lysis syndrome prophylaxis and management. Methemoglobinemia is a serious rare adverse effect of rasburicase, more common in patients with G6PD deficiency. Prompt diagnosis and appropriate management of this condition can make the difference between successful recovery and significant morbidity. Here we discuss the link of rasburicase with methemoglobinemia and the pathophysiology behind increased incidence of this side effect in G6PD deficient patients...
January 11, 2017: Current Drug Safety
https://www.readbyqxmd.com/read/28069005/prognostic-efficacy-of-the-human-b-cell-lymphoma-prognostic-genes-in-predicting-disease-free-survival-dfs-in-the-canine-counterpart
#8
Mohamad Zamani-Ahmadmahmudi, Sina Aghasharif, Keyhan Ilbeigi
BACKGROUND: Canine B-cell lymphoma is deemed an ideal model of human non-Hodgkin's lymphoma where the lymphomas of both species share similar clinical features and biological behaviors. However there are some differences between tumor features in both species. In the current study, we sought to evaluate the prognostic efficacy of human B-cell lymphoma prognostic gene signatures in canine B-cell lymphoma. METHODS: The corresponding probe sets of 36 human B-cell lymphoma prognostic genes were retrieved from 2 canine B-cell lymphoma microarray datasets (GSE43664 and GSE39365) (76 samples), and prognostic probe sets were thereafter detected using the univariate and multivariate Cox proportional-hazard model and the Kaplan-Meier analysis...
January 9, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28059624/pre-clinical-development-of-gene-modification-of-hematopoietic-stem-cells-with-chimeric-antigen-receptors-for-cancer-immunotherapy
#9
Sarah M Larson, Laurel C Truscott, Tzu-Ting Chiou, Amie Patel, Roy Kao, Andy Tu, Tulika Tyagi, Xiang Lu, David Elashoff, Satiro N De Oliveira
Patients with refractory or recurrent B-lineage hematologic malignancies have less than 50% of chance of cure despite intensive therapy and innovative approaches are needed. We hypothesize that gene modification of hematopoietic stem cells (HSC) with an anti-CD19 chimeric antigen receptor (CAR) will produce a multi-lineage, persistent immunotherapy against B-lineage malignancies that can be controlled by the HSVsr39TK suicide gene. High-titer third-generation self-inactivating lentiviral constructs were developed to deliver a second-generation CD19-specific CAR and the herpes simplex virus thymidine kinase HSVsr39TK to provide a suicide gene to allow ablation of gene-modified cells if necessary...
January 6, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28058698/high-soluble-cd30-levels-and-associated-anti-hla-antibodies-in-patients-with-failed-renal-allografts
#10
Gonca E Karahan, Yasar Caliskan, Kursat Ozdilli, Cigdem Kekik, Huseyin Bakkaloglu, Bahar Caliskan, Aydin Turkmen, Mehmet S Sever, Fatma S Oguz
INTRODUCTION: Serum soluble CD30 (sCD30), a 120-kD glycoprotein that belongs to the tumor necrosis factor receptor family, has been suggested as a marker of rejection in kidney transplant patients. The aim of this study was to evaluate the relationship between sCD30 levels and anti-HLA antibodies, and to compare sCD30 levels in patients undergoing hemodialysis (HD) with and without failed renal allografts and transplant recipients with functioning grafts. METHODS: 100 patients undergoing HD with failed grafts (group 1), 100 patients undergoing HD who had never undergone transplantation (group 2), and 100 kidney transplant recipients (group 3) were included in this study...
December 26, 2016: International Journal of Artificial Organs
https://www.readbyqxmd.com/read/28058578/pd-l1-expression-and-tumor-infiltrating-pd-1-%C3%A2-lymphocytes-associated-with-outcome-in-her2-%C3%A2-breast-cancer-patients
#11
Julia Y S Tsang, Wai-Ling Au, Kwan-Yin Lo, Yun-Bi Ni, Thazin Hlaing, Jintao Hu, Siu-Ki Chan, Kui-Fat Chan, Sai-Yin Cheung, Gary M Tse
PURPOSE: Clinical trials showing programmed death (PD)-1-PD-ligand 1 (L1) axis as a promising therapeutic target in melanoma and non-small cell lung cancers have made the pathway a focus of recent attention. However, the data regarding PD-L1/PD-1 in breast cancer are inconsistent. Given the heterogeneity of breast cancers, the clinical relevance of PD-L1 and PD-1 tumor infiltrating lymphocytes (TIL) may vary according to subtypes of breast cancer. We aim to investigate PD-L1 expression in a large cohort of breast cancers and analyze its clinico-pathological as well as outcome relationship according to molecular subtypes...
January 5, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28054442/markers-and-function-of-human-nk-cells-in-normal-and-pathological-conditions
#12
REVIEW
Genny Del Zotto, Emanuela Marcenaro, Paola Vacca, Simona Sivori, Daniela Pende, Mariella Della Chiesa, Francesca Moretta, Tiziano Ingegnere, Maria Cristina Mingari, Alessandro Moretta, Lorenzo Moretta
Natural killer (NK) cells, the most important effectors of the Innate Lymphoid Cells (ILCs), play a fundamental role in tumor immune-surveillance, defense against viruses and, in general, in innate immune responses. NK cell activation is mediated by several activating receptors and co-receptors able to recognize ligands on virus-infected or tumor cells. To prevent healthy cells from auto-aggression, NK cells are provided with strong inhibitory receptors (KIRs and NKG2A) which recognize HLA class I molecules on target cells and, sensing their level of expression, allow killing of targets underexpressing HLA-class I...
January 5, 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/28053195/tcr-based-therapy-for-multiple-myeloma-and-other-b-cell-malignancies-targeting-intracellular-transcription-factor-bob1
#13
Lorenz Jahn, Pleun Hombrink, Renate S Hagedoorn, Michel G D Kester, Dirk M van der Steen, Tania Rodriguez, Tsvetelina Pentcheva-Hoang, Arnoud H de Ru, Marjolein P Schoonakker, Miranda H Meeuwsen, Marieke Griffioen, Peter A van Veelen, J H Frederik Falkenburg, Mirjam H M Heemskerk
Immunotherapy of hematological malignancies or solid tumors by administration of monoclonal antibodies or T-cells engineered to express chimeric antigen receptors or T-cell receptors (TCRs) has demonstrated clinical efficacy. However, antigen-loss tumor escape variants and the absence of currently targeted antigens on several malignancies hampers the widespread application of immunotherapy. We have isolated a TCR targeting a peptide of the intracellular B-cell specific transcription factor BOB1 presented in the context of HLA-B*07:02...
January 4, 2017: Blood
https://www.readbyqxmd.com/read/28052009/cancer-associated-fibroblasts-promote-an-immunosuppressive-microenvironment-through-the-induction-and-accumulation-of-protumoral-macrophages
#14
Hideyuki Takahashi, Koichi Sakakura, Takeshi Kudo, Minoru Toyoda, Kyoichi Kaira, Tetsunari Oyama, Kazuaki Chikamatsu
Stromal cells in the tumor microenvironment (TME) closely interact with tumor cells and affect tumor cell behavior in diverse manners. We herein investigated the mechanisms by which cancer-associated fibroblasts (CAFs) affect the functional polarization of tumor-associated macrophages (TAMs) in oral squamous cell carcinoma (OSCC) in vitro and in human cancer samples. The expression of CD68, CD14, CD163, CD200R, CD206, HLA-G, CD80, and CD86 was higher in CD14-positive cells co-cultured with the culture supernatants of CAFs established from OSCC specimens (CAF-educated cells) than in control cells...
December 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/28039079/post-transplant-cyclophosphamide-and-tacrolimus-mycophenolate-mofetil-combination-prevents-graft-versus-host-disease-in-allogeneic-peripheral-blood-hematopoietic-cell-transplantation-from-hla-identical-donors
#15
Fabrizio Carnevale-Schianca, Daniela Caravelli, Susanna Gallo, Valentina Coha, Lorenzo D'Ambrosio, Elena Vassallo, Marco Fizzotti, Francesca Nesi, Luisa Gioeni, Massimo Berger, Alessandra Polo, Loretta Gammaitoni, Paolo Becco, Lidia Giraudo, Monica Mangioni, Dario Sangiolo, Giovanni Grignani, Delia Rota-Scalabrini, Antonino Sottile, Franca Fagioli, Massimo Aglietta
Allogeneic hematopoietic cell transplant (HCT) remains the only curative therapy for many hematologic malignancies but it is limited by high nonrelapse mortality (NRM), primarily from unpredictable control of graft-versus-host disease (GVHD). Recently, post-transplant cyclophosphamide demonstrated improved GVHD control in allogeneic bone marrow HCT. Here we explore cyclophosphamide in allogeneic peripheral blood stem cell transplantation (alloPBSCT). Patients with high-risk hematologic malignancies received alloPBSCT from HLA-matched unrelated/related donors...
December 27, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28029485/shenfu-injection-for-improving-cellular-immunity-and-clinical-outcome-in-patients-with-sepsis-or-septic-shock
#16
Ning Zhang, Jianhua Liu, Zeliang Qiu, Yiping Ye, Jian Zhang, Tianzheng Lou
PURPOSE: To assess the efficacy of Shenfu injection (SFI) for enhancing cellular immunity and improving the clinical outcomes of patients with septic shock. METHODS: Patients with sepsis were randomly assigned to receive either SFI at a dose of 100mL every 24hours for 7 consecutive days or a placebo in addition to conventional therapy. The immunologic parameters were collected on days 1, 3, and 7 after the above treatments, and the clinical outcomes were updated for 28days...
September 7, 2016: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28026046/anti-lgi1-encephalitis-is-strongly-associated-with-hla-dr7-and-hla-drb4
#17
Agnes van Sonderen, Dave L Roelen, Johannes A Stoop, Robert M Verdijk, Geert W Haasnoot, Roland D Thijs, Paul W Wirtz, Marco W J Schreurs, Frans H J Claas, Peter A E Sillevis Smitt, Maarten J Titulaer
Leucine-rich glioma-inactivated1 (LGI1)-encephalitis is an antibody-associated inflammation of the limbic area. An autoimmune etiology is suspected but not proven yet. We performed HLA-analysis in 25 non-tumor anti-LGI1 patients and discovered a remarkably strong HLA-association. HLA-DR7 was present in 88% compared to 19.6% in healthy controls (p=4.1*10-11). HLA-DRB4 was present in all patients and in 46.5% controls (p=1.19*10-7). These findings support the autoimmune hypothesis. An exploratory analysis was performed in a small group of four tumor-LGI1 patients...
December 27, 2016: Annals of Neurology
https://www.readbyqxmd.com/read/28025979/driving-gene-engineered-t-cell-immunotherapy-of-cancer
#18
REVIEW
Laura A Johnson, Carl H June
Chimeric antigen receptor (CAR) gene-engineered T cell therapy holds the potential to make a meaningful difference in the lives of patients with terminal cancers. For decades, cancer therapy was based on biophysical parameters, with surgical resection to debulk, followed by radiation and chemotherapy to target the rapidly growing tumor cells, while mostly sparing quiescent normal tissues. One breakthrough occurred with allogeneic bone-marrow transplant for patients with leukemia, which provided a sometimes curative therapy...
January 2017: Cell Research
https://www.readbyqxmd.com/read/28025329/association-between-gwas-identified-lung-adenocarcinoma-susceptibility-loci-and-egfr-mutations-in-never-smoking-asian-women-and-comparison-with-findings-from-western-populations
#19
Wei Jie Seow, Keitaro Matsuo, Chao Agnes Hsiung, Kouya Shiraishi, Minsun Song, Hee Nam Kim, Maria Pik Wong, Yun-Chul Hong, H Dean Hosgood, Zhaoming Wang, I-Shou Chang, Jiu-Cun Wang, Nilanjan Chatterjee, Margaret Tucker, Hu Wei, Tetsuya Mitsudomi, Wei Zheng, Jin Hee Kim, Baosen Zhou, Neil E Caporaso, Demetrius Albanes, Min-Ho Shin, Lap Ping Chung, She-Juan An, Ping Wang, Hong Zheng, Yasushi Yatabe, Xu-Chao Zhang, Young Tae Kim, Xiao-Ou Shu, Young-Chul Kim, Bryan A Bassig, Jiang Chang, James Chung Man Ho, Bu-Tian Ji, Michiaki Kubo, Yataro Daigo, Hidemi Ito, Yukihide Momozawa, Kyota Ashikawa, Yoichiro Kamatani, Takayuki Honda, Hiromi Sakamoto, Hideo Kunitoh, Koji Tsuta, Shun-Ichi Watanabe, Hiroshi Nokihara, Yohei Miyagi, Haruhiko Nakayama, Shingo Matsumoto, Masahiro Tsuboi, Koichi Goto, Zhihua Yin, Jianxin Shi, Atsushi Takahashi, Akiteru Goto, Yoshihiro Minamiya, Kimihiro Shimizu, Kazumi Tanaka, Tangchun Wu, Fusheng Wei, Jason Y Y Wong, Fumihiko Matsuda, Jian Su, Yeul Hong Kim, In-Jae Oh, Fengju Song, Victor Ho Fun Lee, Wu-Chou Su, Yuh-Min Chen, Gee-Chen Chang, Kuan-Yu Chen, Ming-Shyan Huang, Pan-Chyr Yang, Hsien-Chih Lin, Yong-Bing Xiang, Adeline Seow, Jae Yong Park, Sun-Seog Kweon, Chien-Jen Chen, Haixin Li, Yu-Tang Gao, Chen Wu, Biyun Qian, Daru Lu, Jianjun Liu, Hyo-Sung Jeon, Chin-Fu Hsiao, Jae Sook Sung, Ying-Huang Tsai, Yoo Jin Jung, Huan Guo, Zhibin Hu, Wen-Chang Wang, Charles C Chung, Charles Lawrence, Laurie Burdett, Meredith Yeager, Kevin B Jacobs, Amy Hutchinson, Sonja I Berndt, Xingzhou He, Wei Wu, Junwen Wang, Yuqing Li, Jin Eun Choi, Kyong Hwa Park, Sook Whan Sung, Li Liu, Chang Hyun Kang, Lingmin Hu, Chung-Hsing Chen, Tsung-Ying Yang, Jun Xu, Peng Guan, Wen Tan, Chih-Liang Wang, Alan Dart Loon Sihoe, Ying Chen, Yi Young Choi, Jen-Yu Hung, Jun Suk Kim, Ho-Il Yoon, Qiuyin Cai, Chien-Chung Lin, In Kyu Park, Ping Xu, Jing Dong, Christopher Kim, Qincheng He, Reury-Perng Perng, Chih-Yi Chen, Roel Vermeulen, Junjie Wu, Wei-Yen Lim, Kun-Chieh Chen, John K C Chan, Minjie Chu, Yao-Jen Li, Jihua Li, Hongyan Chen, Chong-Jen Yu, Li Jin, Yen-Li Lo, Ying-Hsiang Chen, Joseph F Fraumeni, Jie Liu, Taiki Yamaji, Yang Yang, Belynda Hicks, Kathleen Wyatt, Shengchao A Li, Juncheng Dai, Hongxia Ma, Guangfu Jin, Bao Song, Zhehai Wang, Sensen Cheng, Xuelian Li, Yangwu Ren, Ping Cui, Motoki Iwasaki, Taichi Shimazu, Shoichiro Tsugane, Junjie Zhu, Gening Jiang, Ke Fei, Guoping Wu, Li-Hsin Chien, Hui-Ling Chen, Yu-Chun Su, Fang-Yu Tsai, Yi-Song Chen, Jinming Yu, Victoria L Stevens, Ite A Laird-Offringa, Crystal N Marconett, Dongxin Lin, Kexin Chen, Yi-Long Wu, Maria Teresa Landi, Hongbing Shen, Nathaniel Rothman, Takashi Kohno, Stephen J Chanock, Qing Lan
To evaluate associations by EGFR mutation status for lung adenocarcinoma risk among never-smoking Asian women, we conducted a meta-analysis of 11 loci previously identified in genome-wide association studies (GWAS). Genotyping in an additional 10,780 never-smoking cases and 10,938 never-smoking controls from Asia confirmed associations with eight known single nucleotide polymorphisms (SNPs). Two new signals were observed at genome-wide significance (P < 5 x 10(-8)), namely, rs7216064 (17q24.3, BPTF), for overall lung adenocarcinoma risk, and rs3817963 (6p21...
December 26, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/28018010/uveal-melanoma-cell-lines-where-do-they-come-from-an-american-ophthalmological-society-thesis
#20
Martine J Jager, J Antonio Bermudez Magner, Bruce R Ksander, Sander R Dubovy
PURPOSE: To determine whether some of the most often used uveal melanoma cell lines resemble their original tumor. METHODS: Analysis of the literature, patient charts, histopathology, mutations, chromosome status, HLA type, and expression of melanocyte markers on cell lines and their primary tumors. We examined five cell lines and the primary tumors from which they were derived. RESULTS: Four of the five examined primary tumors were unusual: one occupied the orbit, two were recurrences after prior irradiation, and one developed in an eye with a nevus of Ota...
August 2016: Transactions of the American Ophthalmological Society
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