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https://www.readbyqxmd.com/read/29339270/proceedings-from-the-fourth-haploidentical-stem-cell-transplantation-symposium-haplo2016-san-diego-california-december-1-2016
#1
REVIEW
Monzr Al Malki, Richard Jones, Qing Ma, Dean Lee, Yair Reisner, Jeffrey S Miller, Peter Lang, Suradej Hongeng, Parameswaran Hari, Samuel Strober, Jianhua Yu, Richard Maziarz, Domenico Mavilio, Denis-Claude Roy, Chiara Bonini, Richard E Champlin, Ephraim J Fuchs, Stefan O Ciurea
The resurgence of haploidentical stem cell transplantation (HaploSCT) over the last decade is one of the most important advances in the field of hematopoietic stem cell transplantation (HSCT). The modified platforms of T cell depletion either ex vivo (CD34+ selection, 'mega-dose' of purified CD34+ cells, or selective depletion of T-cells) or newer platforms of in vivo depletion of T cells, with either post-transplant high-dose cyclophosphamide (PTCy) or intensified immune suppression, have contributed to better outcomes, with survival that is similar to HLA-match donor transplantation...
January 12, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29331515/mhc-class-i-loaded-ligands-from-breast-cancer-cell-lines-a-potential-hla-i-typed-antigen-collection
#2
Dmitri V Rozanov, Nikita D Rozanov, Kami Chiotti, Ashok Reddy, Phillip A Wilmarth, Larry L David, Seung W Cha, Sunghee Woo, Pavel Pevzner, Vineet Bafna, Gregory G Burrows, Juha K Rantala, Trevor Levin, Pavana Anur, Katie Johnson-Camacho, Shaadi Tabatabaei, Daniel J Munson, Tullia C Bruno, Jill E Slansky, John W Kappler, Naoto Hirano, Sebastian Boegel, Bernard A Fox, Colt Egelston, Diana L Simons, Grecia Jimenez, Peter P Lee, Joe W Gray, Paul T Spellman
To build a catalog of peptides presented by breast cancer cells, we undertook systematic MHC class I immunoprecipitation followed by elution of MHC class I-loaded peptides in breast cancer cells. We determined the sequence of 3196 MHC class I ligands representing 1921 proteins from a panel of 20 breast cancer cell lines. After removing duplicate peptides, i.e., the same peptide eluted from more than one cell line, the total number of unique peptides was 2740. Of the unique peptides eluted, more than 1750 had been previously identified, and of these, sixteen have been shown to be immunogenic...
January 10, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29327110/the-role-of-interleukin-2-all-trans-retinoic-acid-and-natural-killer-cells-surveillance-mechanisms-in-anti-gd2-antibody-therapy-in-neuroblastoma
#3
Rosa Nguyen, Jim Houston, Wing K Chan, David Finkelstein, Michael A Dyer
Although anti-disialoganglioside (GD2) antibodies are successfully used for neuroblastoma therapy, a third of patients with neuroblastoma experience treatment failure or serious toxicity. Various strategies have been employed in the clinic to improve antibody-dependent cell-mediated cytotoxicity (ADCC), such as the addition of interleukin (IL)-2 to enhance natural killer (NK) cell function, adoptive transfer of allogeneic NK cells to exploit immune surveillance, and retinoid-induced differentiation therapy...
January 11, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29317492/a-protein-interaction-network-centered-on-leucine-rich-repeats-and-immunoglobulin-like-domains-1-lrig1-regulates-growth-factor-receptors
#4
Mahmood Faraz, Carl Herdenberg, Camilla Holmlund, Roger Henriksson, Håkan Hedman
Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a tumor suppressor and a negative regulator of several receptor tyrosine kinases (RTKs). The molecular mechanisms by which LRIG1 mediates its tumor suppressor effects and regulates RTKs remain incompletely understood. Here, we performed a yeast two-hybrid screen to identify novel LRIG1-interacting proteins and mined data from the BioPlex (biophysical interactions of ORFeome-based complexes) protein interaction data repository. The putative LRIG1 interactors identified in the screen were functionally evaluated using a triple co-transfection system in which HEK293 cells were co-transfected with platelet-derived growth factor receptor alpha (PDGFRA), LRIG1, and shRNAs against the identified LRIG1 interactors...
January 9, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29314742/the-role-of-mass-spectrometry-and-proteogenomics-in-the-advancement-of-hla-epitope-prediction
#5
REVIEW
Amanda L Creech, Ying S Ting, Scott P Goulding, John Fk Sauld, Dominik Barthelme, Michael S Rooney, Terri A Addona, Jennifer G Abelin
A challenge in developing personalized cancer immunotherapies is the prediction of putative cancer-specific antigens. Currently, predictive algorithms are used to infer binding of peptides to human leukocyte antigen (HLA) heterodimers to aid in the selection of putative epitope targets. One drawback of current epitope prediction algorithms is that they are trained on datasets containing biochemical HLA-peptide binding data that may not completely capture the rules associated with endogenous processing and presentation...
January 3, 2018: Proteomics
https://www.readbyqxmd.com/read/29301752/t-cell-responses-in-the-microenvironment-of-primary-renal-cell-carcinoma-implications-for-adoptive-cell-therapy
#6
Rikke Andersen, Marie Christine Wulff Westergaard, Julie Westerlin Kjeldsen, Anja Mueller, Natasja Wulff Pedersen, Sine Reker Hadrup, Ozcan Met, Barbara Seliger, Bjarne Kromann-Andersen, Thomas Hasselager, Marco Donia, Inge Marie Svane
In vitro expansion of large numbers of highly potent tumor-reactive T cells appears a prerequisite for effective adoptive cell therapy (ACT) with autologous tumor-infiltrating lymphocytes (TIL) as shown in metastatic melanoma (MM). We therefore sought to determine whether renal cell carcinomas (RCC) are infiltrated with tumor-reactive T cells that could be efficiently employed for adoptive transfer immunotherapy. TILs and autologous tumor cell lines (TCLs) were successfully generated from 22 (92%) and 17 (77%) of 24 consecutive primary RCC specimens and compared to those generated from MM...
January 4, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29298343/epcam-peptide-primed-dendritic-cell-vaccination-confers-significant-anti-tumor-immunity-in-hepatocellular-carcinoma-cells
#7
Yoo Jin Choi, Seong-Joon Park, You-Soo Park, Hee Sung Park, Kwang Mo Yang, Kyu Heo
Cancer stem-like cells (CSCs) may play a key role in tumor initiation, self-renewal, differentiation, and resistance to current treatments. Dendritic cells (DCs) play a vital role in host immune reactions as well as antigen presentation. In this study, we explored the suitability of using CSC peptides as antigen sources for DC vaccination against human breast cancer and hepatocellular carcinoma (HCC) with the aim of achieving CSC targeting and enhancing anti-tumor immunity. CD44 is used as a CSC marker for breast cancer and EpCAM is used as a CSC marker for HCC...
2018: PloS One
https://www.readbyqxmd.com/read/29297942/expression-pattern-of-immunosurveillance-related-antigen-in-adult-t-cell-leukemia-lymphoma
#8
Naoko Asano, Hiroaki Miyoshi, Takeharu Kato, Joji Shimono, Noriaki Yoshida, Daisuke Kurita, Yuya Sasaki, Keisuke Kawamoto, Koichi Ohshima, Masao Seto
AIMS: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy with a poor prognosis. Human leukocyte antigen (HLA) and β2M serve as key molecules in tumor immunity, and their expression is frequently reduced in tumor cells. Programmed cell death (PD)-1/PD-ligand1 (PD-L1) interactions play a role in escape of tumor cells from T-cell immunity. Therefore, this study aimed to determine the clinicopathological relevance of HLA and β2M expressions in ATLL cells and PD-L1 expression in lymphoma or stromal cells and predict the overall survival of patients with ATLL...
January 3, 2018: Histopathology
https://www.readbyqxmd.com/read/29296176/predictive-value-of-different-proportion-of-lesion-hla-g-expression-in-colorectal-cancer
#9
Rui-Li Zhang, Xia Zhang, Shan-Shan Dong, Bing Hu, Qiu-Yue Han, Jian-Gang Zhang, Wen-Jun Zhou, Aifen Lin, Wei-Hua Yan
Differential expression of HLA-G has been observed among cancer types and tumors from individuals with the same type of cancer; however, its clinical significance is rather limited. In this study, expression and predictive relevance of HLA-G expression in 457 primary colorectal cancer (CRC, ncolon = 232, nrectal = 225) patients was investigated. Data showed 70.7% (323/457) of the CRC were HLA-G expression when the above 5% (HLA-GLow) was considered as positive, which wasn't associated with patient survival (p = 0...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29288540/expansion-of-human-%C3%AE-%C3%AE-t-cells-for-adoptive-immunotherapy-using-a-bisphosphonate-prodrug
#10
Yoshimasa Tanaka, Kaoru Murata-Hirai, Masashi Iwasaki, Kenji Matsumoto, Kosuke Hayashi, Asuka Kumagai, Mohanad H Nada, Hong Wang, Hirohito Kobayashi, Hiroshi Kamitakahara, Haruki Okamura, Tomoharu Sugie, Nagahiro Minato, Masakazu Toi, Craig T Morita
Cancer immunotherapy with human γδ T cells expressing Vγ2Vδ2 T cell receptor (also termed Vγ9Vδ2) has shown promise because of their ability to recognize and kill most types of tumors in an MHC-unrestricted fashion that is independent of the number of tumor mutations. In clinical trials, adoptive transfer of Vγ2Vδ2 T cells has been shown to be safe and does not require preconditioning. In this report, we describe a method for preparing highly enriched human Vγ2Vδ2 T cells using the bisphosphonate prodrug, tetrakis-pivaloyloxymethyl 2-(thiazole-2-ylamino)ethylidene-1,1-bisphosphonate (PTA)...
December 30, 2017: Cancer Science
https://www.readbyqxmd.com/read/29285385/mhc-class-ii-associated-stomach-cancer-mutations-correlate-with-lack-of-subsequent-tumor-development
#11
John M Yavorski, George Blanck
The role of tumor cell expression of major histocompatibility class II (MHCII) has been controversial, with evidence indicating that tumor cell expression of MHCII may lead to an anti-tumor immune response and to tumor cell apoptosis and that MHCII has pro-tumorigenic functions. The cancer genome atlas (TCGA) indicates numerous deleterious mutations for the highly specific, MHCII transcriptional activation proteins, RFX5, RFXAP, RFXANK and CIITA. Also, mutations in the non-polymorphic, human leukocyte antigen (HLA)-DRA gene, which encodes the heavy chain for the most prominent human MHCII molecule, HLA-DR, are common...
December 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29285306/hla-g-3027-polymorphism-is-associated-with-tumor-relapse-in-pediatric-hodgkin-s-lymphoma
#12
Valli De Re, Laura Caggiari, Lara Mussolin, Emanuele Stefano d'Amore, Barbara Famengo, Mariangela De Zorzi, Lia Martina, Caterina Elia, Marta Pillon, Nicola Santoro, Paola Muggeo, Salvatore Buffardi, Maurizio Bianchi, Alessandra Sala, Piero Farruggia, Luciana Vinti, Edgardo D Carosella, Roberta Burnelli, Maurizio Mascarin
In this study, we tested whether polymorphisms in human leukocyte antigen G (HLA-G) were associated with event-free survival (EFS) in pediatric Hodgkin's lymphoma (HL). We evaluated the association of HLA-G 3'-UTR polymorphisms with EFS in 113 pediatric HL patients treated using the AIEOP LH-2004 protocol. Patients with the +3027-C/A genotype (rs17179101, UTR-7 haplotype) showed lower EFS than those with the +3027-C/C genotype (HR= 3.23, 95%CI: 0.99-10.54, P=0.012). Female patients and systemic B symptomatic patients with the HLA-G +3027 polymorphism showed lower EFS...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29282306/human-m2-macrophages-limit-nk-cell-effector-functions-through-secretion-of-tgf-%C3%AE-and-engagement-of-cd85j
#13
Sol Y Nuñez, Andrea Ziblat, Florencia Secchiari, Nicolás I Torres, Jessica M Sierra, Ximena L Raffo Iraolagoitia, Romina E Araya, Carolina I Domaica, Mercedes B Fuertes, Norberto W Zwirner
NK cells play important roles during immunosurveillance against tumors and viruses as they trigger cytotoxicity against susceptible cells and secrete proinflammatory cytokines such as IFN-γ. In addition, upon activation, macrophages can become proinflammatory (M1) or anti-inflammatory (M2) cells. Although the consequences of the cross-talk between M1 and NK cells are known, the outcome of the cross-talk between M2 and NK cells remains ill-defined. Therefore, in the current work, we investigated the outcome and the underlying mechanisms of the interaction between resting or stimulated human NK cells with M1 or M2...
December 27, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29273955/prognostic-value-of-tumor-stroma-ratio-combined-with-the-immune-status-of-tumors-in-invasive-breast-carcinoma
#14
K M H Vangangelt, G W van Pelt, C C Engels, H Putter, G J Liefers, V T H B M Smit, R A E M Tollenaar, P J K Kuppen, W E Mesker
PURPOSE: Complex interactions occur between cancer cells and cells in the tumor microenvironment. In this study, the prognostic value of the interplay between tumor-stroma ratio (TSR) and the immune status of tumors in breast cancer patients was evaluated. METHODS: A cohort of 574 breast cancer patients was analyzed. The percentage of tumor stroma was visually estimated on Hematoxylin and Eosin (H&E) stained histological tumor tissue sections. Immunohistochemical staining was performed for classical human leukocyte antigen (HLA) class I, HLA-E, HLA-G, markers for regulatory T (Treg) cells, natural killer (NK) cells and cytotoxic T-lymphocytes (CTLs)...
December 22, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29273486/merkel-cell-carcinomas-infiltrated-with-cd33-myeloid-cells-and-cd8-t-cells-are-associated-with-improved-outcome
#15
Thibault Kervarrec, Pauline Gaboriaud, Patricia Berthon, Julia Zaragoza, David Schrama, Roland Houben, Yannick Le Corre, Eva Hainaut-Wierzbicka, Francois Aubin, Guido Bens, Jorge Domenech, Serge Guyétant, Antoine Touzé, Mahtab Samimi
BACKGROUND: Merkel cell carcinoma (MCC) is a rare tumor of the skin with an aggressive behavior. Immunity is the main regulator of MCC development, and many interactions between lymphocytes and tumor cells have been proven. However, the impact of tumor-infiltrating myeloid cells (TIMs) needs better characterization. OBJECTIVE: To characterize TIMs in MCC and their association with other immune effectors and patient outcome. METHODS: MCC cases were reviewed from a historical/prospective cohort...
December 19, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/29261129/lym-1-chimeric-antigen-receptor-t-cells-exhibit-potent-anti-tumor-effects-against-b-cell-lymphoma
#16
Long Zheng, Peisheng Hu, Brandon Wolfe, Caryn Gonsalves, Luqing Ren, Leslie A Khawli, Harvey R Kaslow, Alan L Epstein
T cells expressing chimeric antigen receptors (CARs) recognizing CD19 epitopes have produced remarkable anti-tumor effects in patients with B-cell malignancies. However, cancer cells lacking recognized epitopes can emerge, leading to relapse and death. Thus, CAR T cells targeting different epitopes on different antigens could improve immunotherapy. The Lym-1 antibody targets a conformational epitope of Human Leukocyte Antigen-antigen D Related (HLA-DR) on the surface of human B-cell lymphomas. Lym-1 CAR T cells were thus generated for evaluation of cytotoxic activity towards lymphoma cells in vitro and in vivo...
December 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29238703/characterization-of-alpha-fetoprotein-effects-on-dendritic-cell-and-its-function-as-effector-immune-response-activator
#17
Jeremiah Suryatenggara, Heri Wibowo, Wahyuni Lukita Atmodjo, George Mathew
Tumor antigen alpha-fetoprotein (AFP) can promote immune tolerance toward tumor cells by inducing regulatory functions of the immune system. The purpose of this study was to characterize the effects of AFP on dendritic cells (DC) in their antitumor immune response stimulation and subsequent immune tolerance toward tumor cells. Monocytes were cultured in medium with GM-CSF and IL-4 and incubated for 6 days to generate immature DC (imDC). AFP was added into the treatment group at the beginning of the monocyte-derived DC culture...
2017: Journal of Hepatocellular Carcinoma
https://www.readbyqxmd.com/read/29224003/human-leukocyte-antigen-g-inhibits-the-anti-tumor-effect-of-natural-killer-cells-via-immunoglobulin-like-transcript-2-in-gastric-cancer
#18
Rui Wan, Zi-Wei Wang, Hui Li, Xu-Dong Peng, Guang-Yi Liu, Jun-Ming Ou, An-Qi Cheng
BACKGROUND/AIMS: Human leukocyte antigen-G (HLA-G) plays an important role in inhibiting natural killer (NK) cell function and promoting immune escape. However, the specific mechanism of HLA-G on NK in gastric cancer (GC) remains not well understood. This study investigated the expression of HLA-G in GC and the role of HLA-G-effected NK cells in GC progression. METHODS: HLA-G expression in GC tissues obtained from 49 patients with GC was analyzed by immunohistochemistry and western blot...
December 7, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29217585/patient-hla-class-i-genotype-influences-cancer-response-to-checkpoint-blockade-immunotherapy
#19
Diego Chowell, Luc G T Morris, Claud M Grigg, Jeffrey K Weber, Robert M Samstein, Vladimir Makarov, Fengshen Kuo, Sviatoslav M Kendall, David Requena, Nadeem Riaz, Benjamin Greenbaum, James Carroll, Edward Garon, David M Hyman, Ahmet Zehir, David Solit, Michael Berger, Ruhong Zhou, Naiyer A Rizvi, Timothy A Chan
CD8+ T cell-dependent killing of cancer cells requires efficient presentation of tumor antigens by human leukocyte antigen class I (HLA-I) molecules. However, the extent to which patient-specific HLA-I genotype influences response to anti-PD-1 or anti-CTLA-4 is currently unknown. We determined the HLA-I genotype of 1,535 advanced cancer patients treated with immune checkpoint blockade (ICB). Maximal heterozygosity at HLA-I loci (A, B, and C) improved overall survival after ICB compared to patients who were homozygous for at least one HLA locus...
December 7, 2017: Science
https://www.readbyqxmd.com/read/29216561/design-synthesis-and-evaluation-of-an-anthraquinone-derivative-conjugated-to-myelin-basic-protein-immunodominant-mbp85-99-epitope-towards-selective-immunosuppression
#20
Anthi Tapeinou, Efstathia Giannopoulou, Carmen Simal, Bjarke E Hansen, Haralabos Kalofonos, Vasso Apostolopoulos, Alexios Vlamis-Gardikas, Theodore Tselios
Anthraquinone type compounds, especially di-substituted amino alkylamino anthraquinones have been widely studied as immunosuppressants. The anthraquinone ring is part of mitoxandrone that has been used for the treatment of multiple sclerosis (MS) and several types of tumors. A desired approach for the treatment of MS would be the immunosuppression and elimination of specific T cells that are responsible for the induction of the disease. Herein, the development of a peptide compound bearing an anthraquinone derivative with the potential to specifically destroy the encephalitogenic T cells responsible for the onset of MS is described...
November 24, 2017: European Journal of Medicinal Chemistry
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