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Tumor HLA

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https://www.readbyqxmd.com/read/28315927/hla-dr-expression-in-tumor-epithelium-is-an-independent-prognostic-indicator-in-esophageal-adenocarcinoma-patients
#1
Margaret R Dunne, Adriana J Michielsen, Katie E O'Sullivan, Mary Clare Cathcart, Ronan Feighery, Brendan Doyle, Jenny A Watson, Naoimh J O'Farrell, Narayanasamy Ravi, Elaine Kay, John V Reynolds, Elizabeth J Ryan, Jacintha O'Sullivan
Esophageal adenocarcinoma (EAC) is an aggressive cancer with poor prognosis, and incidence is increasing rapidly in the Western world. Measurement of immune markers has been shown to have prognostic significance in a growing number of cancers, but whether this is true for EAC has yet to be evaluated. This study aimed to characterize HLA-DR expression in the esophagus across the inflammation to cancer progression sequence and to assess the prognostic significance of HLA-DR expression in EAC. Tissue microarrays (TMA) were constructed from esophageal tissue taken from patients at different stages in the cancer progression sequence; normal, esophagitis, Barrett's esophagus (BE), low- and high-grade dysplasia (LGD, HGD) and EAC...
March 18, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28301575/generation-of-murine-tumor-cell-lines-deficient-in-mhc-molecule-surface-expression-using-the-crispr-cas9-system
#2
Krishna Das, David Eisel, Clarissa Lenkl, Ashish Goyal, Sven Diederichs, Elke Dickes, Wolfram Osen, Stefan B Eichmüller
In this study, the CRISPR/Cas9 technology was used to establish murine tumor cell lines, devoid of MHC I or MHC II surface expression, respectively. The melanoma cell line B16F10 and the murine breast cancer cell line EO-771, the latter stably expressing the tumor antigen NY-BR-1 (EO-NY), were transfected with an expression plasmid encoding a β2m-specific single guide (sg)RNA and Cas9. The resulting MHC I negative cells were sorted by flow cytometry to obtain single cell clones, and loss of susceptibility of peptide pulsed MHC I negative clones to peptide-specific CTL recognition was determined by IFNγ ELISpot assay...
2017: PloS One
https://www.readbyqxmd.com/read/28295914/development-of-a-gastric-carcinoid-tumor-following-allogeneic-hematopoietic-stem-cell-transplantation-for-early-t-cell-precursor-acute-lymphoblastic-leukemia
#3
Tsung-Yen Chang, Jin-Yao Lai, Chao-Jan Wang, Shih-Yen Chen, Tang-Her Jaing, Chuen Hsueh, Lee-Yung Shih, Shih-Hsiang Chen
Gastric carcinoid tumor is rarely diagnosed in children. We report a case of gastric carcinoid tumor that occurred after allogeneic HSCT. A 13-year-old girl with ETP acute lymphoblastic leukemia underwent allogeneic HSCT from a 7/8 HLA-matched unrelated donor. She presented with rashes, abdominal pain, and diarrhea, which were suggestive of GVHD, 7 months after HSCT. Immunosuppressive agents failed to resolve these symptoms well. After a series of evaluations, carcinoid syndrome caused by a gastric carcinoid tumor was diagnosed...
March 11, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28294381/cd3-cd8-nkg2d-t-lymphocytes-induce-apoptosis-and-necroptosis-in-hla-negative-cells-via-fasl-fas-interaction
#4
O K Ivanova, T N Sharapova, E A Romanova, L P Sashchenko, D V Yashin
An important problem in cellular immunology is to identify new populations of cytotoxic lymphocytes capable of killing tumor cells that have lost classical components of MHC-machinery and to understand mechanisms of the death of these cells. We have previously found that CD4(+) CD25(+) lymphocytes appear in the lymphokine-activated killer (LAK) cell culture, which carry Tag7 (PGRP-S) and FasL proteins on their surface and can kill Hsp70- and Fas-expressing HLA-negative cells. In this work, we have continued to study the mechanisms of killing of the HLA-negative tumor cells, focusing this time on the CD8+ lymphocytes...
March 15, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28293239/major-histocompatibility-complex-class-i-chain-related-a-mica-molecules-relevance-in-solid-organ-transplantation
#5
REVIEW
Ajay Kumar Baranwal, Narinder K Mehra
An ever growing number of reports on graft rejection and/or failure even with good HLA matches have highlighted an important role of non-HLA antigens in influencing allograft immunity. The list of non-HLA antigens that have been implicated in graft rejection in different types of organ transplantation has already grown long. Of these, the Major Histocompatibility Complex class I chain-related molecule A (MICA) is one of the most polymorphic and extensively studied non-HLA antigenic targets especially in the kidney transplantation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28287509/using-x-ray-crystallography-biophysics-and-functional-assays-to-determine-the-mechanisms-governing-t-cell-receptor-recognition-of-cancer-antigens
#6
Bruce J MacLachlan, Alexander Greenshields-Watson, Georgina H Mason, Andrea J Schauenburg, Valentina Bianchi, Pierre J Rizkallah, Andrew K Sewell, Anna Fuller, David K Cole
Human CD8+ cytotoxic T lymphocytes (CTLs) are known to play an important role in tumor control. In order to carry out this function, the cell surface-expressed T-cell receptor (TCR) must functionally recognize human leukocyte antigen (HLA)-restricted tumor-derived peptides (pHLA). However, we and others have shown that most TCRs bind sub-optimally to tumor antigens. Uncovering the molecular mechanisms that define this poor recognition could aid in the development of new targeted therapies that circumnavigate these shortcomings...
February 6, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28280852/tantigen-a-comprehensive-database-of-tumor-t-cell-antigens
#7
Lars Rønn Olsen, Songsak Tongchusak, Honghuang Lin, Ellis L Reinherz, Vladimir Brusic, Guang Lan Zhang
Tumor T cell antigens are both diagnostically and therapeutically valuable molecules. A large number of new peptides are examined as potential tumor epitopes each year, yet there is no infrastructure for storing and accessing the results of these experiments. We have retroactively cataloged more than 1000 tumor peptides from 368 different proteins, and implemented a web-accessible infrastructure for storing and accessing these experimental results. All peptides in TANTIGEN are labeled as one of the four categories: (1) peptides measured in vitro to bind the HLA, but not reported to elicit either in vivo or in vitro T cell response, (2) peptides found to bind the HLA and to elicit an in vitro T cell response, (3) peptides shown to elicit in vivo tumor rejection, and (4) peptides processed and naturally presented as defined by physical detection...
March 9, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28274688/interleukin-2-and-interleukin-10-function-synergistically-to-promote-cd8-t-cell-cytotoxicity-which-is-suppressed-by-regulatory-t-cells-in-breast-cancer
#8
Xiaogang Li, Ping Lu, Bo Li, Wanfu Zhang, Rong Yang, Yan Chu, Kaiyuan Luo
The precise role of interleukin (IL)-10 in breast cancer is not clear. Previous studies suggested a tumor-promoting role of IL-10 in breast cancer, whereas recent discoveries that IL-10 activated and expanded tumor-resident CD8(+) T cells challenged the traditional view. Here, we investigated the role of IL-10 in HLA-A2-positive breast cancer patients with Grade III, Stage IIA or IIB in-situ and invasive ductal carcinoma, and compared it with that of IL-2, the canonical CD8(+) T cell growth factor. We first observed that breast cancer patients presented higher serum levels of IL-2 and IL-10 than healthy controls...
March 5, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28273004/tcr-like-antibody-drug-conjugates-mediate-killing-of-tumor-cells-with-low-peptide-hla-targets
#9
Devin B Lowe, Camille K Bivens, Alexis S Mobley, Christian E Herrera, Amanda L McCormick, Timea Wichner, Manoj K Sabnani, Laurence M Wood, Jon A Weidanz
The currently marketed antibody-drug conjugates (ADC) destabilize microtubule assembly in cancer cells and initiate apoptosis in patients. However, few tumor antigens (TA) are expressed at high densities on cancer lesions, potentially minimizing the therapeutic index of current ADC regimens. The peptide/human leukocyte antigen (HLA) complex can be specifically targeted by therapeutic antibodies (designated T cell receptor [TCR]-like antibodies) and adequately distinguish malignant cells, but has not been the focus of ADC development...
March 8, 2017: MAbs
https://www.readbyqxmd.com/read/28270499/pd-l1-is-a-therapeutic-target-of-the-bromodomain-inhibitor-jq1-and-combined-with-hla-class-i-a-promising-prognostic-biomarker-in-neuroblastoma
#10
Ombretta Melaiu, Marco Mina, Marco Chierici, Renata Boldrini, Giuseppe Jurman, Paolo Romania, Valerio D'Alicandro, Maria Chiara Benedetti, Aurora Castellano, Tao Liu, Cesare Furlanello, Franco Locatelli, Doriana Fruci
PURPOSE: This study sought to evaluate expression of PD-L1 and HLA class I on neuroblastoma cells and PD-1 and LAG3 on tumor-infiltrating lymphocytes to better define patient risk-stratification and understand whether this tumor may benefit from therapies targeting immune-checkpoint molecules. EXPERIMENTAL DESIGN: In situ immunohistochemical staining for PD-L1, HLA class I, PD-1 and LAG3 was assessed in 77 neuroblastoma specimens, previously characterized for tumor-infiltrating T cell-density, and correlated with clinical outcome...
March 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28264447/the-escape-of-cancer-from-t-cell-mediated-immune-surveillance-hla-class-i-loss-and-tumor-tissue-architecture
#11
REVIEW
Federico Garrido, Francisco Perea, Mónica Bernal, Abel Sánchez-Palencia, Natalia Aptsiauri, Francisco Ruiz-Cabello
Tumor immune escape is associated with the loss of tumor HLA class I (HLA-I) expression commonly found in malignant cells. Accumulating evidence suggests that the efficacy of immunotherapy depends on the expression levels of HLA class I molecules on tumors cells. It also depends on the molecular mechanism underlying the loss of HLA expression, which could be reversible/"soft" or irreversible/"hard" due to genetic alterations in HLA, β2-microglobulin or IFN genes. Immune selection of HLA-I negative tumor cells harboring structural/irreversible alterations has been demonstrated after immunotherapy in cancer patients and in experimental cancer models...
February 27, 2017: Vaccines
https://www.readbyqxmd.com/read/28263240/peptide-pulsed-dendritic-cell-vaccine-in-combination-with-carboplatin-and-paclitaxel-chemotherapy-for-stage-iv-melanoma
#12
Keitaro Fukuda, Takeru Funakoshi, Toshiharu Sakurai, Yoshio Nakamura, Mariko Mori, Keiji Tanese, Akiko Tanikawa, Junichi Taguchi, Tomonobu Fujita, Masato Okamoto, Masayuki Amagai, Yutaka Kawakami
In this study, we aimed to evaluate the feasibility and efficacy of peptide-pulsed dendritic cell (DC) vaccine in combination with carboplatin and paclitaxel chemotherapy (DCCP) for patients with stage IV melanoma previously treated with dacarbazine-containing regimen. Six HLA-A24 and 3 HLA-A02 patients were treated with carboplatin (area under the curve 5) and paclitaxel (175 mg/m) on day 1 and DCs (2×10 cells) pulsed with Wilms tumor gene 1 (WT1), gp100, tyrosinase, and either MAGE-A3 (for HLA-A24) or MAGE-A2 (for HLA-A02) peptides on days 8 and 22 in 28-day cycle for up to three cycles...
March 3, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28260295/-experimental-study-on-the-immune-response-of-fusion-tumor-vaccine-of-hepg2-and-dendritic-cells-in-vitro
#13
Y B Pang, B Y Cui, J He, X P Huang, W Liang, L Q Li, X L Luo
Objective: To estimate the immune response of HepG2/dendritic cell (DC) fusion cells vaccines against HepG2 cells in vitro. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from healthy donors by Ficoll-Hypaque density-gradient centrifugation.Then DC were obtain from PBMCs by culturing in medium containing granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) for 5 days.DC and HepG2 fusion cells were induced by polythyleneglycol (PEG). The fusion cells were examined under fluorescence microscope by labeling DCs and HepG2 with green and red fluorescein, respectively, and then the fusion rates were analyzed by flow cytometry...
February 21, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28254787/serine-proteases-enhance-immunogenic-antigen-presentation-on-lung-cancer-cells
#14
Haley L Peters, Satyendra C Tripathi, Celine Kerros, Hiroyuki Katayama, Haven R Garber, Lisa S St John, Lorenzo Federico, Ismail M Meraz, Jack A Roth, Boris Sepesi, Mourad Majidi, Kathryn Ruisaard, Karen Clise-Dwyer, Jason Roszik, Don L Gibbons, John Heymach, Stephen G Swisher, Chantale Bernantchez, Gheath Alatrash, Samir M Hanash, Jeffrey J Molldrem
Immunotherapies targeting immune checkpoints have proven efficacious in reducing the burden of lung cancer in patients; however, the antigenic targets of these re-invigorated T cells remain poorly defined. Lung cancer tumors contain tumor-associated macrophages (TAM) and neutrophils, which release the serine proteases neutrophil elastase (NE) and proteinase 3 (P3) into the tumor microenvironment. NE and P3 shape the antitumor adaptive immune response in breast cancer and melanoma. In this report, we demonstrate that lung cancer cells cross-presented the tumor-associated antigen PR1, derived from NE and P3...
March 2, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28245875/severe-nivolumab-induced-pneumonitis-preceding-durable-clinical-remission-in-a-patient-with-refractory-metastatic-lung-squamous-cell-cancer-a-case-report
#15
Hong Li, Weijie Ma, Ken Y Yoneda, Elizabeth H Moore, Yanhong Zhang, Lee L Q Pu, Garrett M Frampton, Michael Molmen, Philip J Stephens, Tianhong Li
BACKGROUND: Programmed cell death 1 (PD-1) and its ligand 1 (PD-L1) inhibitors have quickly become standard of care for patients with advanced non-small cell lung cancer and increasing numbers of other cancer types. In this report, we discuss the clinical history, pathological evaluation, and genomic findings in a patient with metastatic lung squamous cell cancer (SCC) who developed severe nivolumab-induced pneumonitis preceding durable clinical remission after three doses of nivolumab...
February 28, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28228754/proofreading-of-peptide-mhc-complexes-through-dynamic-multivalent-interactions
#16
REVIEW
Christoph Thomas, Robert Tampé
The adaptive immune system is able to detect and destroy cells that are malignantly transformed or infected by intracellular pathogens. Specific immune responses against these cells are elicited by antigenic peptides that are presented on major histocompatibility complex class I (MHC I) molecules and recognized by cytotoxic T lymphocytes at the cell surface. Since these MHC I-presented peptides are generated in the cytosol by proteasomal protein degradation, they can be metaphorically described as a window providing immune cells with insights into the state of the cellular proteome...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28214886/adenovirus-vector-harboring-the-hbcag-and-tripeptidyl-peptidase-ii-genes-induces-potent-cellular-immune-responses-in-vivo
#17
Quanhui Tan, Siyuan Ma, Jianjun Hu, Xiaohua Chen, Yongsheng Yu, Zhenghao Tang, Guoqin Zang
BACKGROUND: Chronic hepatitis B virus (HBV) infection is associated with a weak but specific cellular immune response of the host to HBV. Tripeptidyl peptidaseⅡ (TPPⅡ), an intracellular macromolecule and proteolytic enzyme, plays an important complementary and compensatory role for the proteasome during viral protein degradation and major histocompatibility complex class I antigen presentation by inducing a specific cellular immune response in vivo. Based on a previous study, we aimed to explore the role of MHC class I antigen presentation in vivo and the mechanisms that may be involved...
January 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28199754/multinucleated-giant-cell-reaction-in-lower-lip-squamous-cell-carcinoma-a-clinical-morphological-and-immunohistochemical-study
#18
Hellen Bandeira de Pontes Santos, Márcia Cristina da Costa Miguel, Leão Pereira Pinto, Manuel Antonio Gordón-Núñez, Pollianna Muniz Alves, Cassiano Francisco Weege Nonaka
BACKGROUND: Multinucleated giant cell (MGC) reactions have been identified in several malignancies, but their frequency and significance in lower lip squamous cell carcinoma (SCC) are not established. This study evaluated the MGC reactions and their association with clinicopathological parameters in lower lip SCCs. The polarization profile of these cells (M1 or M2 macrophages) was also assessed. METHODS: The presence and distribution of MGC reactions in high-power fields (400×) were evaluated in hematoxylin/eosin-stained histological sections of 91 lower lip SCCs...
February 15, 2017: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/28197391/high-nkg2a-expression-contributes-to-nk-cell-exhaustion-and-predicts-a-poor-prognosis-of-patients-with-liver-cancer
#19
Cheng Sun, Jing Xu, Qiang Huang, Mei Huang, Hao Wen, Chuanshan Zhang, Jinyu Wang, Jiaxi Song, Meijuan Zheng, Haoyu Sun, Haiming Wei, Weihua Xiao, Rui Sun, Zhigang Tian
Background and Aims: As the predominant lymphocyte subset in the liver, natural killer (NK) cells have been shown to be highly associated with the outcomes of patients with chronic hepatitis B virus infection (CHB) and hepatocellular carcinoma (HCC). Previously, we reported that NKG2A, a checkpoint candidate, mediates human and murine NK cell dysfunction in CHB. However, NK cell exhaustion and, particularly, the level of NKG2A expression within liver tumors have not been reported. Methods: In this study, we analyzed NKG2A expression and the related dysfunction of NK cells located in intra- or peritumor regions of liver tissue samples from 207 HCC patients, in addition to analyzing disease outcomes...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28197368/immunosuppressive-cd14-hla-dr-lo-neg-monocytes-are-elevated-in-pancreatic-cancer-and-primed-by-tumor-derived-exosomes
#20
Naureen Javeed, Michael P Gustafson, Shamit K Dutta, Yi Lin, William R Bamlet, Ann L Oberg, Gloria M Petersen, Suresh T Chari, Allan B Dietz, Debabrata Mukhopadhyay
Immunological strategies to treat pancreatic cancer offer new therapeutic approaches to improve patient outcomes. Understanding alterations in the immune systems of pancreatic cancer patients will likely lead to advances in immunotherapy for the disease. We profiled peripheral blood leukocytes from pancreatic cancer patients (n = 22) and age-matched controls (n = 20) using flow cytometry. Immune profiling of pancreatic cancer patients identified phenotypic changes in various immune cell populations, including a population of immunosuppressive monocytes (CD14(+)HLA-DR(lo/neg)), which were shown to be increased in these patients...
2017: Oncoimmunology
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