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https://www.readbyqxmd.com/read/29234329/neoantigens-generated-by-individual-mutations-and-their-role-in-cancer-immunity-and-immunotherapy
#1
REVIEW
Mirjana Efremova, Francesca Finotello, Dietmar Rieder, Zlatko Trajanoski
Recent preclinical and clinical studies have proved the long-standing hypothesis that tumors elicit adaptive immune responses and that the antigens driving effective T-cell response are neoantigens, i.e., peptides that are generated from somatically mutated genes. Hence, the characterization of neoantigens and the identification of the immunogenic ones are of utmost importance for improving cancer immunotherapy and broadening its efficacy to a larger fraction of patients. In this review, we first introduce the methods used for the quantification of neoantigens using next-generation sequencing data and then summarize results obtained using these tools to characterize the neoantigen landscape in solid cancers...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29156566/cgas-sting-pathway-in-cancer-jekyll-and-hyde-story-of-cancer-immune-response
#2
REVIEW
Debojit Bose
The last two decades have witnessed enormous growth in the field of cancer immunity. Mechanistic insights of cancer immunoediting have not only enhanced our understanding but also paved the way to target and/or harness the innate immune system to combat cancer, called cancer immunotherapy. Cyclic GMP-AMP synthase (cGAS)/Stimulator of interferon genes(STING) pathway has recently emerged as nodal player in cancer immunity and is currently being explored as potential therapeutic target. Although therapeutic activation of this pathway has shown promising anti-tumor effects in vivo, evidence also indicates the role of this pathway in inflammation mediated carcinogenesis...
November 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29132146/identification-of-unique-neoantigen-qualities-in-long-term-survivors-of-pancreatic-cancer
#3
Vinod P Balachandran, Marta Łuksza, Julia N Zhao, Vladimir Makarov, John Alec Moral, Romain Remark, Brian Herbst, Gokce Askan, Umesh Bhanot, Yasin Senbabaoglu, Daniel K Wells, Charles Ian Ormsby Cary, Olivera Grbovic-Huezo, Marc Attiyeh, Benjamin Medina, Jennifer Zhang, Jennifer Loo, Joseph Saglimbeni, Mohsen Abu-Akeel, Roberta Zappasodi, Nadeem Riaz, Martin Smoragiewicz, Z Larkin Kelley, Olca Basturk, Mithat Gönen, Arnold J Levine, Peter J Allen, Douglas T Fearon, Miriam Merad, Sacha Gnjatic, Christine A Iacobuzio-Donahue, Jedd D Wolchok, Ronald P DeMatteo, Timothy A Chan, Benjamin D Greenbaum, Taha Merghoub, Steven D Leach
Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors, yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using whole-exome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8(+) T-cell infiltrates, but neither alone, stratified patients with the longest survival...
November 8, 2017: Nature
https://www.readbyqxmd.com/read/29107334/mhc-i-genotype-restricts-the-oncogenic-mutational-landscape
#4
Rachel Marty, Saghar Kaabinejadian, David Rossell, Michael J Slifker, Joris van de Haar, Hatice Billur Engin, Nicola de Prisco, Trey Ideker, William H Hildebrand, Joan Font-Burgada, Hannah Carter
MHC-I molecules expose the intracellular protein content on the cell surface, allowing T cells to detect foreign or mutated peptides. The combination of six MHC-I alleles each individual carries defines the sub-peptidome that can be effectively presented. We applied this concept to human cancer, hypothesizing that oncogenic mutations could arise in gaps in personal MHC-I presentation. To validate this hypothesis, we developed and applied a residue-centric patient presentation score to 9,176 cancer patients across 1,018 recurrent oncogenic mutations...
October 20, 2017: Cell
https://www.readbyqxmd.com/read/29054996/nivolumab-induces-tumor-evolution-in-patients-with-melanoma
#5
(no author information available yet)
Nivolumab treatment results in immunoediting and loss of tumor cells expressing neoantigens.
October 20, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29032503/cd4-and-cd8-t-lymphocyte-interplay-in-controlling-tumor-growth
#6
REVIEW
Dmitrij Ostroumov, Nora Fekete-Drimusz, Michael Saborowski, Florian Kühnel, Norman Woller
The outstanding clinical success of immune checkpoint blockade has revived the interest in underlying mechanisms of the immune system that are capable of eliminating tumors even in advanced stages. In this scenario, CD4 and CD8 T cell responses are part of the cancer immune cycle and both populations significantly influence the clinical outcome. In general, the immune system has evolved several mechanisms to protect the host against cancer. Each of them has to be undermined or evaded during cancer development to enable tumor outgrowth...
October 14, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28924054/immunosurveillance-and-immunoediting-of-breast-cancer-via-class-i-mhc-receptors
#7
Megan M Tu, Mir Munir A Rahim, Céline Sayed, Ahmad Bakur Mahmoud, Andrew P Makrigiannis
Ly49 receptors, which recognize "self" class I major histocompatibility complex (MHC-I) molecules, enable natural killer (NK) cells to detect loss of MHC-I expression on transformed and virally infected cells. The impact of NK cell-mediated MHC-I surveillance on immunoediting of breast cancer is still not fully understood. This work assesses the impact of Ly49 receptors on tumor development in terms of cancer control and in driving immune-evading cancer mutations. Genetically modified Ly49-deficient mice and those lacking NK cells through antibody depletion were less able to control E0771-derived mammary tumors in an MHC-I-dependent fashion...
September 18, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28920005/the-frequency-of-neoantigens-per-somatic-mutation-rather-than-overall-mutational-load-or-number-of-predicted-neoantigens-per-se-is-a-prognostic-factor-in-ovarian-clear-cell-carcinoma
#8
Hirokazu Matsushita, Kosei Hasegawa, Katsutoshi Oda, Shogo Yamamoto, Akira Nishijima, Yuichi Imai, Kayo Asada, Yuji Ikeda, Takahiro Karasaki, Keiichi Fujiwara, Hiroyuki Aburatani, Kazuhiro Kakimi
Neoantigens derived from tumor-specific somatic mutations are excellent targets for anti-tumor immune responses. In ovarian clear cell carcinoma (OCCC), checkpoint blockade yields durable responses in a subset of patients. To approach the question of why only some patients respond, we first investigated neoantigen loads and immune signatures using exome sequencing and expression array data for 74 OCCC patients treated conventionally. Neither the number of missense mutations nor total predicted neoantigens assessed in the tumor correlated with clinical outcomes...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28914398/characteristics-and-prognosis-of-breast-cancer-after-liver-or-kidney-transplantation
#9
I-Ji Jeong, Sung-Gyu Lee, Young Hoon Kim, Beom Seok Ko, Jong Won Lee, Byung Ho Son, Se-Hyun Ahn, Hee Jeong Kim
PURPOSE: Immunoediting is crucial in cancer development and progression. This study compared the characteristics and prognosis of post-transplant breast cancer (PTBC) patients receiving immunosuppressants and general breast cancer patients. METHODS: Data from the Asan Medical Center Breast Cancer (AMCBC), kidney transplantation, and liver transplantation databases recorded during 1989-2013 were retrospectively analyzed. Four controls of AMCBC cohort per one case of PTBC cohort were selected based on tumor size, lymph node metastasis, and age...
September 15, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28845161/targeting-cancer-stem-cells-and-their-niche-current-therapeutic-implications-and-challenges-in-pancreatic-cancer
#10
REVIEW
Jiangang Zhao, Jiahui Li, Hans A Schlößer, Felix Popp, Marie Christine Popp, Hakan Alakus, Karl-Walter Jauch, Christiane J Bruns, Yue Zhao
Cancer stem cells (CSCs) have been identified as a subpopulation of stem-like cancer cells with the ability of self-renewal and differentiation in hematological malignancies and solid tumors. Pancreatic cancer is one of the most lethal cancers worldwide. CSCs are thought to be responsible for cancer initiation, progression, metastasis, chemoresistance, and recurrence in pancreatic cancer. In this review, we summarize the characteristics of pancreatic CSCs and discuss the mechanisms involved in resistance to chemotherapy, the interactions with the niche, and the potential role in cancer immunoediting...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28759799/quantitative-and-qualitative-analysis-of-regulatory-t-cells-in-b-cell-chronic-lymphocytic-leukemia
#11
Vassiliki E Mpakou, Heleni-Dikaia Ioannidou, Eugene Konsta, Myrofora Vikentiou, Aris Spathis, Frieda Kontsioti, Christos K Kontos, Athanassios D Velentzas, Sotiris Papageorgiou, Diamantina Vasilatou, Konstantinos Gkontopoulos, Irene Glezou, Georgia Stavroulaki, Efthimia Mpazani, Stella Kokkori, Elias Kyriakou, Petros Karakitsos, George Dimitriadis, Vasiliki Pappa
Accumulated data indicate a significant role of T cell dysfunction in the pathogenesis of chronic lymphocytic leukemia. In CLL, regulatory T cells are significantly higher and show lower apoptotic levels compared to healthy donors. We demonstrate that CLL derived CD4(+)CD25(-)CD127(-) and CD4(+)CD25(low)CD127(-) subpopulations share a common immunophenotypic profile with conventional Tregs and are associated with advanced stage disease. We further provide evidence that the increased number of Tregs contributes indirectly to the proliferation of the CLL clone, by suppressing the proliferation of Teffs which in turn suppress CLL cells...
September 2017: Leukemia Research
https://www.readbyqxmd.com/read/28716899/hdac1-upregulation-by-nanog-promotes-multidrug-resistance-and-a-stem-like-phenotype-in-immune-edited-tumor-cells
#12
Kwon-Ho Song, Chel Hun Choi, Hyo-Jung Lee, Se Jin Oh, Seon Rang Woo, Soon-Oh Hong, Kyung Hee Noh, Hanbyoul Cho, Eun Joo Chung, Jae-Hoon Kim, Joon-Yong Chung, Stephen M Hewitt, Seungki Baek, Kyung-Mi Lee, Cassian Yee, Minjoo Son, Chih-Ping Mao, T C Wu, Tae Woo Kim
Cancer immunoediting drives the adaptation of tumor cells to host immune surveillance. Immunoediting driven by antigen (Ag)-specific T cells enriches NANOG expression in tumor cells, resulting in a stem-like phenotype and immune resistance. Here, we identify HDAC1 as a key mediator of the NANOG-associated phenotype. NANOG upregulated HDAC1 through promoter occupancy, thereby decreasing histone H3 acetylation on K14 and K27. NANOG-dependent, HDAC1-driven epigenetic silencing of cell-cycle inhibitors CDKN2D and CDKN1B induced stem-like features...
September 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28680538/a-tumor-specific-antibody-to-aid-breast-cancer-screening-in-women-with-dense-breast-tissue
#13
Lopamudra Das Roy, Lloye M Dillon, Ru Zhou, Laura J Moore, Chad Livasy, Joe M El-Khoury, Rahul Puri, Pinku Mukherjee
Screening for breast cancer has predominantly been done using mammography. Unfortunately, mammograms miss 50% cancers in women with dense breast tissue. Multi-modal screenings offer the best chance of enhancing breast cancer screening effectiveness. We evaluated the use of TAB004, an antibody that recognizes the tumor form of the glycoprotein MUC1 (tMUC1), to aid early detection of breast cancer. Our experimental approach was to follow tMUC1 from the tissue into circulation. We found that 95% of human breast cancer tissues across all subtypes stained positive for TAB004...
March 2017: Genes & Cancer
https://www.readbyqxmd.com/read/28660480/dendritic-cell-based-immunotherapy-a-basic-review-and-recent-advances
#14
REVIEW
João Constantino, Célia Gomes, Amílcar Falcão, Bruno Miguel Neves, Maria Teresa Cruz
Dendritic cells (DCs) are considered a very promising arm to activate the immune system in immunotherapeutic strategies against cancer. DCs are the most powerful antigen-presenting cells (APCs), being highly efficient at generating robust immune responses. They are also considered the center of the immune system, since they provide a crucial link between both innate and adaptive immune responses. Thus, DC-based cancer immunotherapy aims to take advantage of these unique characteristics of DCs to better fight cancer...
August 2017: Immunologic Research
https://www.readbyqxmd.com/read/28659412/uncovering-the-underlying-mechanism-of-cancer-tumorigenesis-and-development-under-an-immune-microenvironment-from-global-quantification-of-the-landscape
#15
Li Wenbo, Jin Wang
The study of the cancer-immune system is important for understanding tumorigenesis and the development of cancer and immunotherapy. In this work, we build a comprehensive cancer-immune model including both cells and cytokines to uncover the underlying mechanism of cancer immunity based on landscape topography. We quantify three steady-state attractors, normal state, low cancer state and high cancer state, for the innate immunity and adaptive immunity of cancer. We also illustrate the cardinal inhibiting cancer immunity interactions and promoting cancer immunity interactions through global sensitivity analysis...
June 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/28611201/relationship-of-the-breast-ductal-carcinoma-in-situ-immune-microenvironment-with-clinicopathological-and-genetic-features
#16
Shona Hendry, Jia-Min B Pang, David J Byrne, Sunil R Lakhani, Margaret C Cummings, Ian G Campbell, G Bruce Mann, Kylie L Gorringe, Stephen B Fox
Purpose: The immune microenvironment of breast ductal carcinoma in situ (DCIS) has yet to be fully explored, and the relationship of immune cells to genetic features of DCIS is unknown.Experimental Design: We quantified tumor associated lymphocytes (TIL) and evaluated PD-L1 protein levels by immunohistochemistry in a cohort of pure DCIS (138 and 79 cases, respectively), some of which had copy number (n = 55) and mutation data (n = 20).Results: TILs were identified in the stroma surrounding DCIS (119/138, 86%) and present at a median TIL score of 5% (range, 0%-90%)...
June 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28595838/deciphering-the-loop-of-epithelial-mesenchymal-transition-inflammatory-cytokines-and-cancer-immunoediting
#17
REVIEW
Antonella Sistigu, Francesca Di Modugno, Gwenola Manic, Paola Nisticò
Tumorigenesis and tumor progression relies on the dialectics between tumor cells, the extracellular matrix and its remodelling enzymes, neighbouring cells and soluble cues. The host immune response is crucial in eliminating or promoting tumor growth and the reciprocal coevolution of tumor and immune cells, during disease progression and in response to therapy, shapes tumor fate by activating innate and adaptive mechanisms. The phenotypic plasticity is a common feature of epithelial and immune cells and epithelial-mesenchymal transition (EMT) is a dynamic process, governed by microenvironmental stimuli, critical in tumor cell shaping, increased tumor cell heterogeneity and stemness...
May 31, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28585539/il-21-mediated-reversal-of-nk-cell-exhaustion-facilitates-anti-tumour-immunity-in-mhc-class-i-deficient-tumours
#18
Hyungseok Seo, Insu Jeon, Byung-Seok Kim, Myunghwan Park, Eun-Ah Bae, Boyeong Song, Choong-Hyun Koh, Kwang-Soo Shin, Il-Kyu Kim, Kiyoung Choi, Taegwon Oh, Jiyoun Min, Byung Soh Min, Yoon Dae Han, Suk-Jo Kang, Sang Joon Shin, Yeonseok Chung, Chang-Yuil Kang
During cancer immunoediting, loss of major histocompatibility complex class I (MHC-I) in neoplasm contributes to the evasion of tumours from host immune system. Recent studies have demonstrated that most natural killer (NK) cells that are found in advanced cancers are defective, releasing the malignant MHC-I-deficient tumours from NK-cell-dependent immune control. Here, we show that a natural killer T (NKT)-cell-ligand-loaded tumour-antigen expressing antigen-presenting cell (APC)-based vaccine effectively eradicates these advanced tumours...
June 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28585308/immunosurveillance-profile-of-oral-squamous-cell-carcinoma-and-oral-epithelial-dysplasia-through-dendritic-and-t-cell-analysis
#19
Ana Carolina Amorim Pellicioli, Lynne Bingle, Paula Farthing, Márcio Ajudarte Lopes, Manoela Domingues Martins, Pablo Agustin Vargas
Oral squamous cell carcinomas (OSCCs) can arise from potentially malignant disorders, such as leukoplakia. The immune system plays an important role recognizing tumour precursor cells. However, due to immuno-editing mechanisms cancer cells are able to escape immune system surveillance. OBJECTIVE: To evaluate the profile of dendritic (Langerhans and plasmacytoid) and T cells in OSCC and oral epithelial dysplasia (OED) and correlate these findings with clinical data. MATERIALS AND METHODS: Fifty cases of OSCC and 48 of OED were immunostained for CD1a and CD83 dendritic Langerhans cells (DLC), CD303 plasmacytoid dendritic cells (pDC) and CD8 followed by quantitative analysis...
June 5, 2017: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/28527911/cancer-stem-cells-at-the-forefront-of-personalized-medicine-and-immunotherapy
#20
REVIEW
Micol E Fiori, Lidia Villanova, Ruggero De Maria
Cancer stem cells (CSCs) represent the main target of the current efforts to eradicate cancer, because of their ability to promote metastatic dissemination and survive cytotoxic therapies. Here, we highlight the potential of patient-derived CSCs as an in vitro and in vivo pre-clinical model and of liquid biopsy as a diagnostic, prognostic and predictive tool. We discuss recently developed therapeutic strategies aiming at specifically targeting the cancer stem cell population, particularly focusing on the latest advances in cancer immunotherapy...
May 18, 2017: Current Opinion in Pharmacology
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