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Tumor HLA

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https://www.readbyqxmd.com/read/28537924/genetic-defects-of-the-irf1-mediated-major-histocompatibility-complex-class-i-antigen-presentation-pathway-occur-prevalently-in-the-jak2-gene-in-non-small-cell-lung-cancer
#1
Tao Shen, Zhengming Chen, Zhizhuang Joe Zhao, Jie Wu
Recognition of major histocompatibility complex (MHC) class I antigens on tumor cells by cytotoxic T cells is involved in T cell-mediated tumor immune surveillance and immune checkpoint therapy. The interferon-γ (IFNγ)-IRF1 signaling pathway regulates MHC class I antigen presentation. To examine genetic defects of the IFNγ-IRF1 pathway in non-small cell lung cancer (NSCLC), we analyzed The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LuAd) and lung squamous cell carcinoma (LuSc) data. Loss-of-function (LOF) genetic alterations of the IFNγ-IRF1 pathway genes (IFNGR1, IFNGR2, JAK1, JAK2, STAT1, IRF1) were found in 64 (6...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28536458/epigenetic-priming-restores-the-hla-class-i-antigen-processing-machinery-expression-in-merkel-cell-carcinoma
#2
Cathrin Ritter, Kaiji Fan, Annette Paschen, Sine Reker Hardrup, Soldano Ferrone, Paul Nghiem, Selma Ugurel, David Schrama, Jürgen C Becker
Merkel cell carcinoma (MCC) is a rare and aggressive, yet highly immunogenic skin cancer. The latter is due to its viral or UV-associated carcinogenesis. For tumor progression MCC has to escape the host's immuno-surveillance, e.g. by loss of HLA class-I expression. Indeed, a reduced HLA class-I expression was observed in MCC tumor tissues and MCC cell lines. This reduced HLA class-I surface expression is caused by an impaired expression of key components of the antigen processing machinery (APM), including LMP2 and LMP7 as well as TAP1 and TAP2...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28536262/in-silico-and-cell-based-analyses-reveal-strong-divergence-between-prediction-and-observation-of-t-cell-recognized-tumor-antigen-t-cell-epitopes
#3
Julien Schmidt, Philippe Guillaume, Danijel Dojcinovic, Julia Karbach, George Coukos, Immanuel Luescher
Tumor exomes provide comprehensive information on mutated, over-expressed genes and aberrant splicing, which can be exploited for personalized cancer immunotherapy. Of particular interest are mutated tumor antigen T cell epitopes, because neoepitope specific T cells often are tumoricidal. However, identifying tumor-specific T cell epitopes is a major challenge. A widely used strategy relies on initial prediction of human leukocyte antigen binding peptides by in silico algorithms, but the predictive power of this approach is unclear...
May 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28533942/hla-a24-ligandome-analysis-of-colon-and-lung-cancer-cells-identifies-a-novel-cancer-testis-antigen-and-a-neoantigen-that-elicits-specific-and-strong-ctl-responses
#4
Vitaly Kochin, Takayuki Kanaseki, Serina Tokita, Sho Miyamoto, Yosuke Shionoya, Yasuhiro Kikuchi, Daichi Morooka, Yoshihiko Hirohashi, Tomohide Tsukahara, Kazue Watanabe, Shingo Toji, Yasuo Kokai, Noriyuki Sato, Toshihiko Torigoe
This study focused on HLA-A24 and comprehensively analyzed the ligandome of colon and lung cancer cells without the use of MHC-binding in silico prediction algorithms. Affinity purification using the antibody specific to HLA-A24 followed by LC-MS/MS sequencing was used to detect peptides, which harbored the known characteristics of HLA-A24 peptides in terms of length and anchor motifs. Ligandome analysis demonstrated the natural presentation of two different types of novel tumor-associated antigens. The ligandome contained a peptide derived from SUV39H2, a gene found to be expressed in a variety of cancers but not in normal tissues (except for the testis)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28523518/decreased-human-leukocyte-antigen-a-02-01-frequency-is-associated-with-risk-of-glioma-and-existence-of-human-cytomegalovirus-a-case-control-study-in-northern-china
#5
Sheng Han, Jian Deng, Zixun Wang, Huan Liu, Wen Cheng, Anhua Wu
BACKGROUND: Human leukocyte antigens (HLAs) play an important role in host defense against viral infection and tumorigenesis. Human cytomegalovirus (HCMV) has been linked to glioma development. This study investigated the relationship between HLA distribution, presence of HCMV, and glioma development in a Han Chinese population. METHODS: The study population included 150 glioma patients and 150 tumor-free brain injury control subjects (control-A) matched according to geography, ethnicity, age, and gender...
May 18, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28521443/loss-of-fas-expression-and-high-expression-of-hla-e-promoting-the-immune-escape-of-early-colorectal-cancer-cells
#6
Renxiang Huang, Dongyang Zhang, Feng Li, Zili Xiao, Meiling Wu, Dongyun Shi, Ping Xiang, Zhijun Bao
Previous studies have investigated the mechanisms of immune evasion of tumor cells in numerous types of advanced solid malignant tumor, and several types of immune preparations have been administered as antitumor adjuvant therapies. However, in the majority of studies, the efficacy of therapies has been revealed to be limited. The present study aimed to investigate the immune evasion mechanisms employed by early colorectal cancer cells and the expression of the molecules associated with immune evasion during the malignant transformation process of normal colorectal epithelial cells to measure the effects of immune intervention for early colorectal cancer, and to improve the efficacy of immunotherapy...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28507809/t-cell-therapy-targeting-a-public-neoantigen-in-microsatellite-instable-colon-cancer-reduces-in-vivo-tumor-growth
#7
Else M Inderberg, Sébastien Wälchli, Marit R Myhre, Sissel Trachsel, Hilde Almåsbak, Gunnar Kvalheim, Gustav Gaudernack
T-cell receptor (TCR) transfer is an attractive strategy to increase the number of cancer-specific T cells in adoptive cell therapy. However, recent clinical and pre-clinical findings indicate that careful consideration of the target antigen is required to limit the risk of off-target toxicity. Directing T cells against mutated proteins such as frequently occurring frameshift mutations may thus be a safer alternative to tumor-associated self-antigens. Furthermore, such frameshift mutations result in novel polypeptides allowing selection of TCRs from the non-tolerant T-cell repertoire circumventing the problem of low affinity TCRs due to central tolerance...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507805/generation-and-functional-characterization-of-mdsc-like-cells
#8
Annkristin Heine, Stefanie Andrea Erika Held, Jonas Schulte-Schrepping, Julia Friederike Andrea Wolff, Kathrin Klee, Thomas Ulas, Niklas Arndt Schmacke, Solveig Nora Daecke, Kati Riethausen, Joachim L Schultze, Peter Brossart
Myeloid-derived suppressor cells (MDSC) are critical in regulating immune responses by suppressing antigen presenting cells (APC) and T cells. We previously observed that incubation of peripheral blood monocytes with interleukin (IL)-10 during their differentiation to monocyte-derived dendritic cells (moDCs) results in the generation of an APC population with a CD14(+)HLA-DR(low)phenotype (IL-10-APC) with reduced stimulatory capacity similar to human MDSC. Co-incubation experiments now revealed that the addition of IL-10-APC to moDC caused a reduction of DC-induced T-cell proliferation, of the expression of maturation markers, and of secreted cytokines and chemokines such as TNF-α, IL-6, MIP-1α and Rantes...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507804/hla-dependent-immune-escape-mechanisms-in-b-cell-lymphomas-implications-for-immune-checkpoint-inhibitor-therapy
#9
Marcel Nijland, Rianne N Veenstra, Lydia Visser, Chuanhui Xu, Kushi Kushekhar, Gustaaf W van Imhoff, Philip M Kluin, Anke van den Berg, Arjan Diepstra
Antigen presentation by tumor cells in the context of Human Leukocyte Antigen (HLA) is generally considered to be a prerequisite for effective immune checkpoint inhibitor therapy. We evaluated cell surface HLA class I, HLA class II and cytoplasmic HLA-DM staining by immunohistochemistry (IHC) in 389 classical Hodgkin lymphomas (cHL), 22 nodular lymphocyte predominant Hodgkin lymphomas (NLPHL), 137 diffuse large B-cell lymphomas (DLBCL), 39 primary central nervous system lymphomas (PCNSL) and 19 testicular lymphomas...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507791/the-mutational-status-of-p53-can-influence-its-recognition-by-human-t-cells
#10
Katerina Shamalov, Shlomo N Levy, Miryam Horovitz-Fried, Cyrille J Cohen
p53 was reported to be an attractive immunotherapy target because it is mutated in approximately half of human cancers, resulting in its inactivation and often accumulation in tumor cells. Peptides derived from p53 are presented by class I MHC molecules and may act as tumor-associated epitopes which could be targeted by p53-specific T cells. Interestingly, it was recently shown that there is a lack of significant correlation between p53 expression levels in tumors and their recognition by p53-TCR transduced T cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28506304/characterization-of-genetic-aberrations-in-a-single-case-of-metastatic-thymic-adenocarcinoma
#11
Yeonghun Lee, Sehhoon Park, Se-Hoon Lee, Hyunju Lee
BACKGROUND: Thymic adenocarcinoma is an extremely rare subtype of thymic epithelial tumors. Due to its rarity, there is currently no sequencing approach for thymic adenocarcinoma. METHODS: We performed whole exome and transcriptome sequencing on a case of thymic adenocarcinoma and performed subsequent validation using Sanger sequencing. RESULTS: The case of thymic adenocarcinoma showed aggressive behaviors with systemic bone metastases. We identified a high incidence of genetic aberrations, which included somatic mutations in RNASEL, PEG10, TNFSF15, TP53, TGFB2, and FAT1...
May 15, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28487238/the-recipient-ccr5-variation-predicts-survival-outcomes-after-bone-marrow-transplantation
#12
Tomohiro Horio, Shohei Mizuno, Kaori Uchino, Motonori Mizutani, Ichiro Hanamura, J Luis Espinoza, Makoto Onizuka, Koichi Kashiwase, Yasuo Morishima, Takahiro Fukuda, Yoshihisa Kodera, Noriko Doki, Koichi Miyamura, Takehiko Mori, Akiyoshi Takami
The chemokine receptor CCR5 plays roles in the trafficking of effector cells towards the site of inflammation. We retrospectively examined the impact of the CCR5 variation (rs1800023, -2086A>G) on transplant outcomes in a cohort of 329 patients who underwent unrelated HLA-matched bone marrow transplantation (BMT) for hematologic malignancies through the Japan Marrow Donor Program. A multivariate analysis showed that the recipient CCR5 -2086A/A genotype was significantly associated with a lower relapse rate but not with the development of graft-versus-host disease (GVHD) or transplant-related mortality, thereby resulting in better disease-free and overall survival rates than other variations...
May 6, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28486273/zebularine-treatment-induces-mage-a11-expression-and-improves-ctl-cytotoxicity-using-a-novel-identified-hla-a2-restricted-mage-a11-peptide
#13
Jiandong Zhang, Meixiang Sang, Lina Gu, Fei Liu, Weijing Li, Danjing Yin, Yunyan Wu, Shina Liu, Weina Huang, Baoen Shan
Melanoma-associated antigen-A11 (MAGE-A11) is frequently expressed in breast cancer and is associated with poor prognosis. Therefore, MAGE-A11 is a potential immunotherapy target in breast cancer. MAGE-A11 expression, however, is downregulated in many patients, thus constraining the application of immunotherapy. The induction of MAGE-A11 expression is crucial for the recognition and killing of breast cancer cells by cytotoxic T lymphocytes (CTL). In this study, a series of HLA-A2-restricted candidate MAGE-A11 peptides were predicted, synthesized, and tested...
May 8, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28472085/transcriptomic-immunologic-signature-associated-with-favorable-clinical-outcome-in-basal-like-breast-tumors
#14
Sandra Martínez-Canales, Francisco Cifuentes, Miguel López De Rodas Gregorio, Leticia Serrano-Oviedo, Eva María Galán-Moya, Eitan Amir, Atanasio Pandiella, Balázs Győrffy, Alberto Ocaña
BACKGROUND: Most patients with early stage triple negative breast cancer (TNBC) receive adjuvant chemotherapy. Activation of the immune system is associated with tumor response and may help identify TNBC with favorable outcome. METHODS: Gene expression data were obtained from the GEO Dataset GDS2250/GSE3744. Affymetrix CEL files were downloaded and analyzed with Affymetrix Transcriptome Analysis Console 3.0. Functional genomics was implemented with David Bioinformatics Resources 6...
2017: PloS One
https://www.readbyqxmd.com/read/28470686/tumor-cell-expression-of-immune-inhibitory-molecules-and-tumor-infiltrating-lymphocyte-count-predict-cancer-specific-survival-in-pancreatic-and-ampullary-cancer
#15
Kostandinos Sideras, Katharina Biermann, Kevin Yap, Shanta Mancham, Patrick P C Boor, Bettina E Hansen, Hans J A Stoop, Maikel P Peppelenbosch, Casper H van Eijck, Stefan Sleijfer, Jaap Kwekkeboom, Marco J Bruno
Understanding the mechanisms of immune resistance in pancreatic and ampullary cancers is crucial for the development of suitable biomarkers and effective immunotherapeutics. Our aim was to examine the expression of the immune inhibiting molecules PD-L1, Galectin-9, HVEM, IDO and HLA-G, as well as CD8+ and FoxP3+ tumor infiltrating lymphocytes (TIL), in pancreatic and ampullary cancers, and to relate their individual, as well as their combined expression, to cancer survival. Tumor tissue from 224 patients with resected pancreatic (n = 148) and ampullary (n = 76) cancer was used to construct tissue-microarrays...
May 3, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28468826/neuropilin-1-mediates-neutrophil-elastase-uptake-and-cross-presentation-in-breast-cancer-cells
#16
Celine Kerros, Satyendra C Tripathi, Dongxing Zha, Jennifer M Mehrens, Anna Sergeeva, Anne V Philips, Na Qiao, Haley L Peters, Hiroyuki Katayama, Pariya Sukhumalchandra, Kathryn E Ruisaard, Alexander A Perakis, Lisa S St John, Sijie Lu, Elizabeth A Mittendorf, Karen Clise-Dwyer, Amanda C Herrmann, Gheath Alatrash, Carlo Toniatti, Samir M Hanash, Qing Ma, Jeffrey J Molldrem
Neutrophil elastase (NE) can be rapidly taken up by tumor cells that lack endogenous NE expression, including breast cancer, which results in cross-presentation of PR1, an NE-derived HLA-A2-restricted peptide that is an immunotherapy target in hematological and solid tumor malignancies. The mechanism of NE uptake, however, remains unknown. Using the mass spectometry-based approach, we identify neuropilin-1 (NRP1) as a NE receptor that mediates uptake and PR1 cross-presentation in breast cancer cells. We demonstrated that soluble NE is a specific, high-affinity ligand for NRP1 with a calculated Kd=38...
May 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28459074/leaps-vaccine-incorporating-her-2-neu-epitope-elicits-protection-that-prevents-and-limits-tumor-growth-and-spread-of-breast-cancer-in-a-mouse-model
#17
Ken S Rosenthal, Sarah Stone, Gary Koski, Daniel H Zimmerman
The prototype J-LEAPS T cell vaccine for HER-2/neu breast cancer (J-HER) consists of the murine HER-2/neu66-74 H-2(d) CD8 T cell epitope covalently attached through a triglycine linker to the J-immune cell binding ligand (ICBL) (human β2 microglobulin38-50 peptide). The J-ICBL was chosen for its potential to promote Th1/Tc1 responses. In this proof-of-concept study, the ability of J-HER to prevent or treat cancer was tested in the TUBO cell-challenged BALB/c mouse model for HER-2/neu-expressing tumors. The J-HER vaccine was administered as an emulsion in Montanide ISA-51 without the need for a more potent adjuvant...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28456791/nk-cells-and-multiple-myeloma-associated-endothelial-cells-molecular-interactions-and-influence-of-il-27
#18
Alessandra Dondero, Beatrice Casu, Francesca Bellora, Angelo Vacca, Annunziata De Luisi, Maria Antonia Frassanito, Claudia Cantoni, Silvia Gaggero, Daniel Olive, Alessandro Moretta, Cristina Bottino, Roberta Castriconi
Angiogenesis represents a hallmark of tumor progression in Multiple Myeloma (MM), a still incurable malignancy. Here we analyzed the activity of cytokine-stimulated NK cells against tumor-associated endothelial cells isolated from bone marrow aspirates of MM patients with active disease (MMECs). We show that NK cells activated with optimal doses of IL-15 killed MMECs thanks to the concerted action of multiple activating receptors. In particular, according to the high expression of PVR and Nectin-2 on MMECs, DNAM-1 actively participated in target recognition...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28454377/frequent-expression-of-human-leukocyte-antigen-class-i-and-the-status-of-intratumoral-immune-cells-in-alveolar-soft-part-sarcoma
#19
Akira Ogose, Hiroyuki Kawashima, Tetsuo Hotta, Takashi Ariizumi, Tetsuro Yamagishi, Naoki Oike, Taro Sasaki, Hiroshi Hatano, Hajime Umezu, Naoto Endo
The prognosis of alveolar soft part sarcoma is poor, despite the slow growth of the tumor. A number of cases with spontaneous regression of this rare tumor have been reported. Although the mechanisms underlying spontaneous regression remain uncertain, local immune reaction may be a possible contributing factor. Immunohistochemical expression of human leukocyte antigen (HLA) class I, cluster of differentiation (CD) 3, CD4, CD8, CD20, CD45, CD56, CD68, CD138 and CD163 were assessed in a series of 10 alveolar soft part sarcomas, and the expression profiles were associated with patients' clinicopathological parameters...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28454277/monocyte-derived-dendritic-cells-from-patients-with-cervical-intraepithelial-lesions
#20
Angela Maria Moed Lopes, Márcia Antoniazi Michelin, Eddie Fernando Cândido Murta
Immunotherapy with dendritic cells (DCs) is a great promise for the treatment of neoplasms. However, the obtainment and protocol of differentiation of these cells may depend on extrinsic factors such as the tumor itself. The aim of the present study was to verify the influence of cervical neoplasia on different protocols of differentiation of monocyte-derived DCs resulting in an increased maturation phenotype. A total of 83 women were included in the study. The patients were grouped in low-grade squamous intraepithelial lesion (LSIL) (n=30), high-grade squamous intraepithelial lesion (HSIL) (n=22), cervical cancer (n=10) and healthy patients (n=21) groups...
March 2017: Oncology Letters
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