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https://www.readbyqxmd.com/read/29869436/understanding-immune-tolerance-of-cancer-re-purposing-insights-from-fetal-allografts-and-microbes
#1
REVIEW
Megan B Barnet, Prunella Blinman, Wendy Cooper, Michael J Boyer, Steven Kao, Christopher C Goodnow
Cancer cells seem to exploit mechanisms that evolves as part of physiological tolerance, which is a complementary and often beneficial form of defense. The study of physiological systems of tolerance can therefore provide insights into the development of a state of host tolerance of cancer, and how to break it. Analysis of these models has the potential to improve our understanding of existing immunological therapeutic targets, and help to identify future targets and rational therapeutic combinations. The treatment of cancer with immune checkpoint inhibitors aims to reverse the progression to tolerance of cancer, and achieve an immunogenic, rather than tolerogenic, homeostasis...
June 4, 2018: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/29793087/skin-allografting-activates-anti-tumor-immunity-and-suppresses-growth-of-colon-cancer-in-mice
#2
Xiang Li, Xu Lan, Grace Wang, Yi Liu, Ke Zhao, Shan-Zheng Lu, Xiao-Xi Xu, Gang-Gang Shi, Kui Ye, Bao-Ren Zhang, Yi-Ming Zhao, Hong-Qiu Han, Cai-Gan Du, Thomas E Ichim, Hao Wang
INTRODUCTION: The tumor cells could escape from the immune elimination through the immunoediting mechanisms including the generation of immunosuppressive or immunoregulative cells. By contrast, allograft transplantation could activate the immune system and induce a strong allogenic response. The aim of this study was to investigate the efficacy of allogenic skin transplantation in the inhibition of tumor growth through the activation of allogenic immune response. METHODS: Full-thickness skin transplantation was performed from C57BL/6 (H-2b ) donors to BALB/c (H-2d ) recipients that were receiving subcutaneous injection of isogenic CT26 colon cancer cells (2 × 106 cells) at the same time...
May 21, 2018: Translational Oncology
https://www.readbyqxmd.com/read/29719409/prediction-of-tumor-mutation-burden-in-breast-cancer-based-on-the-expression-of-er-pr-her-2-and-ki-67
#3
Junnan Xu, Xiangyu Guo, Mingxi Jing, Tao Sun
Objective: Cancer immunoediting is the process of eliminating highly immunogenic tumor cells by somatic evolution and protecting the host from tumor development in the host immune system. Frequencies of somatic mutations or tumor mutation burden (TMB) were associated with immunogenicity of breast cancer. This study aimed to predict the level of TMB in patients with breast cancer by the expression of estrogen (ER), progesterone (PR), HER-2, and Ki-67, thereby anticipating the prognosis of patients and the possible response to immunotherapy...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29708132/the-evolving-understanding-of-immunoediting-and-the-clinical-impact-of-immune-escape
#4
EDITORIAL
Caroline E McCoach, Trever G Bivona
No abstract text is available yet for this article.
March 2018: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29678688/control-in-dormancy-or-eradication-of-cancer-stem-cells-mathematical-modeling-and-stability-issues
#5
Walid Djema, Catherine Bonnet, Frédéric Mazenc, Jean Clairambault, Emilia Fridman, Pierre Hirsch, François Delhommeau
OBJECTIVE: Modeling and analysis of cell population dynamics enhance our understanding of cancer. Here we introduce and explore a new model that may apply to many tissues. ANALYSES: An age-structured model describing coexistence between mutated and ordinary stem cells is developed and explored. The model is transformed into a nonlinear time-delay system governing the dynamics of healthy cells, coupled to a nonlinear differential-difference system describing dynamics of unhealthy cells...
July 14, 2018: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29643764/the-idh1-mutation-induced-oncometabolite-2-hydroxyglutarate-may-affect-dna-methylation-and-expression-of-pd-l1-in-gliomas
#6
Luyan Mu, Yu Long, Changlin Yang, Linchun Jin, Haipeng Tao, Haitao Ge, Yifan E Chang, Aida Karachi, Paul S Kubilis, Gabriel De Leon, Jiping Qi, Elias J Sayour, Duane A Mitchell, Zhiguo Lin, Jianping Huang
Background: Malignant gliomas are heterogeneous brain tumors with the potential for aggressive disease progression, as influenced by suppressive immunoediting. Given the success and enhanced potential of immune-checkpoint inhibitors in immunotherapy, we focused on the connections between genetic alterations affected by IDH1 mutations and immunological landscape changes and PDL-1 expression in gliomas. Methods: Paired surgically resected tumors from lower-grade gliomas (LGGs) and glioblastomas (GBM) were investigated, and a genetic analysis of patients' primary tumor samples culled from TCGA datasets was performed...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29546344/local-immunotherapy-of-cancer-innovative-approaches-to-harnessing-tumor-specific-immune-responses
#7
Vivek Murthy, Janna Minehart, Daniel H Sterman
Modern cancer immunotherapies represent a major shift in paradigm with respect to how we understand innate and adaptive responses to malignancy. Successful tumors co-opt normal immunosurveillance mechanisms by potent interactions between the tumor and local draining lymph nodes. Tumor cells mediate a complex and dynamic immunoediting procedure that results in increased vascular efflux into the draining lymphatics, an immunosuppressive microenvironment rich in regulatory T-lymphocytes, dysfunctional antigen presentation, and downregulation of normal effector lymphocyte responses...
December 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29527223/pten-at-the-interface-of-immune-tolerance-and-tumor-suppression
#8
Andrew Brandmaier, Sheng-Qi Hou, Sandra Demaria, Silvia C Formenti, Wen H Shen
BACKGROUND: PTEN is well known to function as a tumor suppressor that antagonizes oncogenic signaling and maintains genomic stability. The PTEN gene is frequently deleted or mutated in human cancers and the wide cancer spectrum associated with PTEN deficiency has been recapitulated in a variety of mouse models of Pten deletion or mutation. Pten mutations are highly penetrant in causing various types of spontaneous tumors that often exhibit resistance to anticancer therapies including immunotherapy...
June 2017: Frontiers in Biology
https://www.readbyqxmd.com/read/29510987/genetic-mechanisms-of-immune-evasion-in-colorectal-cancer
#9
Catherine S Grasso, Marios Giannakis, Daniel K Wells, Tsuyoshi Hamada, Xinmeng Jasmine Mu, Michael Quist, Jonathan A Nowak, Reiko Nishihara, Zhi Rong Qian, Kentaro Inamura, Teppei Morikawa, Katsuhiko Nosho, Gabriel Abril-Rodriguez, Charles Connolly, Helena Escuin-Ordinas, Milan S Geybels, William M Grady, Li Hsu, Siwen Hu-Lieskovan, Jeroen R Huyghe, Yeon Joo Kim, Paige Krystofinski, Mark D M Leiserson, Dennis J Montoya, Brian B Nadel, Matteo Pellegrini, Colin C Pritchard, Cristina Puig-Saus, Elleanor H Quist, Ben J Raphael, Stephen J Salipante, Daniel Sanghoon Shin, Eve Shinbrot, Brian Shirts, Sachet Shukla, Janet L Stanford, Wei Sun, Jennifer Tsoi, Alexander Upfill-Brown, David A Wheeler, Catherine J Wu, Ming Yu, Syed H Zaidi, Jesse M Zaretsky, Stacey B Gabriel, Eric S Lander, Levi A Garraway, Thomas J Hudson, Charles S Fuchs, Antoni Ribas, Shuji Ogino, Ulrike Peters
To understand the genetic drivers of immune recognition and evasion in colorectal cancer, we analyzed 1,211 colorectal cancer primary tumor samples, including 179 classified as microsatellite instability-high (MSI-high). This set includes The Cancer Genome Atlas colorectal cancer cohort of 592 samples, completed and analyzed here. MSI-high, a hypermutated, immunogenic subtype of colorectal cancer, had a high rate of significantly mutated genes in important immune-modulating pathways and in the antigen presentation machinery, including biallelic losses of B2M and HLA genes due to copy-number alterations and copy-neutral loss of heterozygosity...
March 6, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29469956/ifn-%C3%AE-orchestrates-tumor-elimination-tumor-dormancy-tumor-escape-and-progression
#10
REVIEW
Hussein F Aqbi, Matthew Wallace, Samay Sappal, Kyle K Payne, Masoud H Manjili
Tumor immunoediting consisting of three phases of elimination, equilibrium or dormancy, and escape has been supported by preclinical and clinical data. A comprehensive understanding of the molecular mechanisms by which antitumor immune responses regulate these three phases are important for developing highly tailored immunotherapeutics that can control cancer. To this end, IFN-γ produced by Th1 cells, cytotoxic T cells, NK cells, and NKT cells is a pleiotropic cytokine that is involved in all three phases of tumor immunoediting, as well as during inflammation-mediated tumorigenesis processes...
February 22, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29449224/natural-killer-receptor-ligand-expression-on-acute-myeloid-leukemia-impacts-survival-and-relapse-after-chemotherapy
#11
Sara Mastaglio, Eric Wong, Travis Perera, Jane Ripley, Piers Blombery, Mark J Smyth, Rachel Koldej, David Ritchie
Natural killer (NKs) cells provide rapid responses to viral-infected and malignant cells, including acute myeloid leukemia (AML) blasts. The balance among inhibitory and activating signals, delivered by multiple interactions between ligands on target cells and NK receptors, determines the posture of the NK cell response to either one of target cell elimination or tolerance. The aim of this work was to study the influence of the differential expression of activating and inhibitory NK receptor ligands (NKRLs) by leukemic blasts on clinical outcome in newly diagnosed AML patients...
February 27, 2018: Blood Advances
https://www.readbyqxmd.com/read/29444931/complete-remission-with-reduction-of-high-risk-clones-following-haploidentical-nk-cell-therapy-against-mds-and-aml
#12
Andreas T Björklund, Mattias Carlsten, Ebba Sohlberg, Lisa L Liu, Trevor Clancy, Mohsen Karimi, Sarah Cooley, Jeffrey S Miller, Monika Klimkowska, Marie Schaffer, Emma Watz, Kristina Wikström, Pontus Blomberg, Björn Engelbrekt Wahlin, Marzia Palma, Lotta Hansson, Per Ljungman, Eva Hellström-Lindberg, Hans-Gustaf Ljunggren, Karl-Johan Malmberg
Purpose: To evaluate the safety, efficacy, and immunobiological correlates of allogeneic NK-cell-based therapy in primary chemotherapy-refractory or relapsed high-risk myelodysplastic syndrome (MDS), secondary AML (MDS/AML), and de novo AML patients. Experimental Design: Sixteen patients received fludarabine/cyclophosphamide conditioning combined with total lymphoid irradiation followed by adoptive immunotherapy with IL2-activated haploidentical NK cells. Results: NK-cell infusions were well-tolerated, with only transient adverse events observed in the 16 patients...
April 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29421984/current-state-and-future-prospects-of-immunotherapy-for-glioma
#13
Neha Kamran, Mahmoud S Alghamri, Felipe J Nunez, Diana Shah, Antonela S Asad, Marianela Candolfi, David Altshuler, Pedro R Lowenstein, Maria G Castro
There is a large unmet need for effective therapeutic approaches for glioma, the most malignant brain tumor. Clinical and preclinical studies have enormously expanded our knowledge about the molecular aspects of this deadly disease and its interaction with the host immune system. In this review we highlight the wide array of immunotherapeutic interventions that are currently being tested in glioma patients. Given the molecular heterogeneity, tumor immunoediting and the profound immunosuppression that characterize glioma, it has become clear that combinatorial approaches targeting multiple pathways tailored to the genetic signature of the tumor will be required in order to achieve optimal therapeutic efficacy...
February 1, 2018: Immunotherapy
https://www.readbyqxmd.com/read/29338608/immunotherapy-of-cancer-targeting-cancer-during-active-disease-or-during-dormancy
#14
Syed Ammer Shah, Melika Zarei, Saeed H Manjili, Georgi Guruli, Xiang-Yang Wang, Masoud H Manjili
Immunotherapeutic targeting of advanced stage cancers has prolonged the survival of cancer patients, yet its curative efficacy is limited due to tumor immunoediting and escape. On the other hand, human vaccines have been able to eradicate smallpox and control several other infectious diseases. The success has resulted from the administration of vaccines in prophylactic settings, or during latency periods in order to protect an individual during future exposure to the disease rather than curing an established disease...
September 2017: Immunotherapy
https://www.readbyqxmd.com/read/29296022/targeting-immune-checkpoints-potentiates-immunoediting-and-changes-the-dynamics-of-tumor-evolution
#15
Mirjana Efremova, Dietmar Rieder, Victoria Klepsch, Pornpimol Charoentong, Francesca Finotello, Hubert Hackl, Natascha Hermann-Kleiter, Martin Löwer, Gottfried Baier, Anne Krogsdam, Zlatko Trajanoski
The cancer immunoediting hypothesis postulates a dual role of the immune system: protecting the host by eliminating tumor cells, and shaping the tumor by editing its genome. Here, we elucidate the impact of evolutionary and immune-related forces on editing the tumor in a mouse model for hypermutated and microsatellite-instable colorectal cancer. Analyses of wild-type and immunodeficient RAG1 knockout mice transplanted with MC38 cells reveal that upregulation of checkpoint molecules and infiltration by Tregs are the major tumor escape mechanisms...
January 2, 2018: Nature Communications
https://www.readbyqxmd.com/read/29285320/immune-system-and-melanoma-biology-a-balance-between-immunosurveillance-and-immune-escape
#16
REVIEW
Anna Passarelli, Francesco Mannavola, Luigia Stefania Stucci, Marco Tucci, Francesco Silvestris
Melanoma is one of the most immunogenic tumors and its relationship with host immune system is currently under investigation. Many immunomodulatory mechanisms, favoring melanomagenesis and progression, have been described to interfere with the disablement of melanoma recognition and attack by immune cells resulting in immune resistance and immunosuppression. This knowledge produced therapeutic advantages, such as immunotherapy, aiming to overcome the immune evasion. Here, we review the current advances in cancer immunoediting and focus on melanoma immunology, which involves a dynamic interplay between melanoma and immune system, as well as on effects of "targeted therapies" on tumor microenvironment for combination strategies...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29282694/immune-checkpoint-blockade-in-breast-cancer-therapy
#17
Xia Bu, Yihui Yao, Xiaoyu Li
Cancer immunotherapy is emerging as the most promising novel strategy for cancer treatment. Cancer immunotherapy is broadly categorized into three forms: immune checkpoint modulation, adoptive cell transfer, and cancer vaccine. Immune checkpoint blockade is demonstrated as the most clinically effective treatment with low immune-related adverse events (irAE). Blockade of PD-1/PD-L1 and CTLA-4 has achieved remarkable success in treating various types of tumors, which sparks great interests in this therapeutic strategy and expands the role of immune checkpoint blockade in treating tumors including breast cancer...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29234329/neoantigens-generated-by-individual-mutations-and-their-role-in-cancer-immunity-and-immunotherapy
#18
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
#19
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
#20
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 23, 2017: Nature
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