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Domenico Ribatti
The immune system plays a major role in the surveillance against tumors. To avoid attack from the immune system, tumor cells develop different strategies to escape immune surveillance. Evidence of immune surveillance comes from both animal models and clinical observations. Mice with a wide variety of immunodeficiencies have a high rate of tumor incidence and are more susceptible to transplanted or chemical carcinogen-induced tumors. Immunosuppressed patients have a high incidence of tumors. However, many patients develop cancer even in the presence of an apparently normal immune system...
October 18, 2016: Oncotarget
Paul Zolkind, Gavin P Dunn, Tianxiang Lin, Malachi Griffith, Obi L Griffith, Ravindra Uppaluri
The recent success of immunotherapies has demonstrated the potency of tumor-specific immune cells in mediating tumor rejection and generating durable tumor immunity. Our understanding of the scientific basis of these responses results from the confluence of a better comprehension of the cancer immunoediting process and the revolution in next generation sequencing of cancer genomes. Recent evidence suggests that T cell specificity for cancer cell expressed mutant proteins - termed neoantigens - is an important component of immune mediated tumor rejection...
October 14, 2016: Oral Oncology
Rebecca A Evans, Mark S Diamond, Andrew J Rech, Timothy Chao, Max W Richardson, Jeffrey H Lin, David L Bajor, Katelyn T Byrne, Ben Z Stanger, James L Riley, Nune Markosyan, Rafael Winograd, Robert H Vonderheide
In carcinogen-driven cancers, a high mutational burden results in neoepitopes that can be recognized immunologically. Such carcinogen-induced tumors may evade this immune response through "immunoediting," whereby tumors adapt to immune pressure and escape T cell-mediated killing. Many tumors lack a high neoepitope burden, and it remains unclear whether immunoediting occurs in such cases. Here, we evaluated T cell immunity in an autochthonous mouse model of pancreatic cancer and found a low mutational burden, absence of predicted neoepitopes derived from tumor mutations, and resistance to checkpoint immunotherapy...
September 8, 2016: JCI Insight
Lucy M De La Cruz, Nadia F Nocera, Brian J Czerniecki
HER2/neu is expressed in the majority of in situ breast cancers, but maintained in 20-30% of invasive breast cancer (IBC). During breast tumorigenesis, there is a progressive loss of anti-HER2 CD4(pos) Th1 (anti-HER2Th1) from benign to ductal carcinoma in situ, with almost complete loss in IBC. This anti-HER2Th1 response can predict response to neoadjuvant therapy, risk of recurrence and disease-free survival. Vaccines consisting of HER2-pulsed type I polarized dendritic cells (DC1) administered during ductal carcinoma in situ and early IBC can efficiently correct anti-HER2Th1 response and have clinical impact on the disease...
October 2016: Immunotherapy
Masoud H Manjili, Savannah E Butler
The immunogenic tumor dormancy has been demonstrated in animal models of cancer, which can explain clinical observations such as an increased incidence of cancer following organ transplantation. The role of immune cell populations in the maintenance of, or escape from, tumor dormancy and subsequent recurrence is poorly understood. Here, we provide a review of literature related to the contribution of Tregs in tumor dormancy or recurrence. Based on clinical results, we suggest that anecdotal reports on the association of human Tregs with poor prognosis are circumstantial rather than implying a cause-effect direction...
September 7, 2016: Immunological Investigations
Yu Lei, Yuying Xie, Yee Sun Tan, Mark E Prince, Jeffrey S Moyer, Jacques Nör, Gregory T Wolf
Evidence gleaned from recent studies on the role of tumor-infiltrating lymphocytes (TILs) suggests that cancer is not only a genetic disease but also an immunologic disease. Head and Neck Squamous Cell Carcinoma (HNSCC) has been a significant model to study cancer cell-immune cell interactions. First, immune cell infiltration is an important feature of these tumors. Second, HNSCC frequently develops resistance to immunogenic cytotoxicity, which provides a window to decipher how tumors engage the immune system to establish immune tolerance...
October 2016: Oral Oncology
Antonella Maglietta, Rosalia Maglietta, Teresa Staiano, Ramona Bertoni, Nicola Ancona, Giancarlo Marra, Leonardo Resta
Little is known about the immunoediting process in precancerous lesions. We explored this aspect of benign colorectal adenomas with a descriptive analysis of the immune pathways and immune cells whose regulation is linked to the morphology and size of these lesions. Two series of polypoid and nonpolypoid colorectal adenomas were used in this study: 1) 84 samples (42 lesions, each with matched samples of normal mucosa) whose gene expression data were used to quantify the tumor morphology- and size-related dysregulation of immune pathways collected in the Molecular Signature Database, using Gene Set Enrichment Analysis; 2) 40 other lesions examined with immunohistochemistry to quantify the presence of immune cells in the stromal compartment...
2016: PloS One
Jennifer J Peterson, Susan K Steele-Moses
BACKGROUND: Immunotherapy has had a long history in cancer treatment and, with recent breakthroughs, new drugs are available that have shown promising results. OBJECTIVES: The current article discusses an overview of immune function, including immunoediting and the theory of immune checkpoints, as well as specific drugs that have been approved as immune checkpoint inhibitors. Additional discussion includes a review of nursing implications and administration, side effects, adverse events, and the future of immuno-oncology...
August 1, 2016: Clinical Journal of Oncology Nursing
Alfredo Perales-Puchalt, Nikolaos Svoronos, Melanie R Rutkowski, Michael J Allegrezza, Amelia J Tesone, Kyle K Payne, Jayamanna Wickramasinghe, Jenny M Nguyen, Shane W O'Brien, Kiranmai Gumireddy, Qihong Huang, Mark Cadungog, Denise C Connolly, Julia Tchou, Tyler J Curiel, Jose R Conejo-Garcia
PURPOSE: Define the safety and effectiveness of T-cells re-directed against Follicle-Stimulating Hormone Receptor (FSHR)-expressing ovarian cancer cells. EXPERIMENTAL DESIGN: FSHR expression was determined by Western-blot, immunohistochemistry and Q-PCR in 77 human ovarian cancer specimens from 6 different histological subtypes and 20 human healthy tissues. The effectiveness of human T-cells targeted with full-length FSH in vivo was determined against a panel of patient-derived xenografts...
July 19, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Neha Kamran, Alexandra Calinescu, Marianela Candolfi, Mayuri Chandran, Yohei Mineharu, Antonela S Asad, Carl Koschmann, Felipe J Nunez, Pedro R Lowenstein, Maria G Castro
INTRODUCTION: Outcome for glioma (GBM) remains dismal despite advances in therapeutic interventions including chemotherapy, radiotherapy and surgical resection. The overall survival benefit observed with immunotherapies in cancers such as melanoma and prostate cancer has fuelled research into evaluating immunotherapies for GBM. AREAS COVERED: Preclinical studies have brought a wealth of information for improving the prognosis of GBM and multiple clinical studies are evaluating a wide array of immunotherapies for GBM patients...
October 2016: Expert Opinion on Biological Therapy
Els M E Verdegaal, Noel F C C de Miranda, Marten Visser, Tom Harryvan, Marit M van Buuren, Rikke S Andersen, Sine R Hadrup, Caroline E van der Minne, Remko Schotte, Hergen Spits, John B A G Haanen, Ellen H W Kapiteijn, Ton N Schumacher, Sjoerd H van der Burg
Recognition of neoantigens that are formed as a consequence of DNA damage is likely to form a major driving force behind the clinical activity of cancer immunotherapies such as T-cell checkpoint blockade and adoptive T-cell therapy. Therefore, strategies to selectively enhance T-cell reactivity against genetically defined neoantigens are currently under development. In mouse models, T-cell pressure can sculpt the antigenicity of tumours, resulting in the emergence of tumours that lack defined mutant antigens...
August 4, 2016: Nature
Fernando Concha-Benavente, Raghvendra Srivastava, Soldano Ferrone, Robert L Ferris
Experimental as well as clinical studies demonstrate that the immune system plays a major role in controlling generation and progression of tumors. The cancer immunoediting theory supports the notion that tumor cell immunogenicity is dynamically shaped by the immune system, as it eliminates immunogenic tumor cells in the early stage of the disease and then edits their antigenicity. The end result is the generation of a tumor cell population able to escape from immune recognition and elimination by tumor infiltrating lymphocytes...
July 2016: Oral Oncology
Christoph Domschke, Andreas Schneeweiss, Stefan Stefanovic, Markus Wallwiener, Joerg Heil, Joachim Rom, Christof Sohn, Philipp Beckhove, Florian Schuetz
More recently, immunotherapy has emerged as a novel potentially effective therapeutic option also for solid malignancies such as breast cancer (BC). Relevant approaches, however, are determined by the 2 main elements of cancer immunoediting - the elimination of nascent transformed cells by immunosurveillance on the one hand and tumor immune escape on the other hand. Correspondingly, we here review the role of the various cellular immune players within the host-protective system and dissect the mechanisms of immune evasion leading to tumor progression...
April 2016: Breast Care
Saravanan Raju, Lena Z Kretzmer, Olivia I Koues, Jacqueline E Payton, Eugene M Oltz, Amanda Cashen, Bojan Polic, Robert D Schreiber, Andrey S Shaw, Mary A Markiewicz
It is now clear that recognition of nascent tumors by the immune system is critical for survival of the host against cancer. During cancer immunoediting, the ability of the tumor to escape immune recognition is important for tumor development. The immune system recognizes tumors via the presence of classical Ags and also by conserved innate mechanisms. One of these mechanisms is the NKG2D receptor that recognizes ligands whose expression is induced by cell transformation. In this study, we show that in NKG2D receptor-deficient mice, increasing numbers of B cells begin to express NKG2D ligands as they age...
June 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Anna Merlo, Silvia Dalla Santa, Riccardo Dolcetti, Paola Zanovello, Antonio Rosato
Immune selective pressure occurring during cancer immunoediting shapes tumor features revealed at clinical presentation. However, in the "Escape" phase, the tumor itself has the chance to influence the immunological response. Therefore, the capacity of the immune response to sculpt the tumor characteristics is only one side of the coin and even the opposite is likely true, i.e. that an antigen can shape the immune response in a sort of "reverse immunoediting". This reciprocal modeling probably occurs continuously, whenever the immune system encounters a tumor/foreign antigen, and can be operative in the pathogen/immune system interplay, thus possibly permeating the protective immunity as a whole...
April 27, 2016: Immunology Letters
Fabian Echterdiek, Jonas Janikovits, Laura Staffa, Meike Müller, Bernd Lahrmann, Monika Frühschütz, Benjamin Hartog, Nina Nelius, Axel Benner, Mirjam Tariverdian, Magnus von Knebel Doeberitz, Niels Grabe, Matthias Kloor
Microsatellite instability (MSI-H) is caused by DNA mismatch repair deficiency and occurs in 15% of colorectal cancers. MSI-H cancers generate highly immunogenic frameshift peptide (FSP) antigens, which elicit pronounced local immune responses. A subset of MSI-H colorectal cancers develops in frame of Lynch syndrome, which represents an ideal human model for studying the concept of immunoediting. Immunoediting describes how continuous anti-tumoral immune surveillance of the host eventually leads to the selection of tumor cells that escape immune cell recognition and destruction...
February 2016: Oncoimmunology
Gabriel A Rabinovich, José R Conejo-García
Along with the discovery of tumor-driven inflammatory pathways, there has been a considerable progress over the past 10years in understanding the mechanisms leading to cancer immunosurveillance and immunoediting. Several regulatory pathways, typically involved in immune cell homeostasis, are co-opted by cancer cells to thwart the development of effective antitumor responses. These regulatory circuits include the engagement of inhibitory checkpoint pathways (CTLA-4, PD-1/PD-L1, LAG-3 and TIM-3), secretion of immunosuppressive cytokines (TGF-β, IL-10), and expansion and/or recruitment of myeloid or lymphoid regulatory cell populations...
August 14, 2016: Journal of Molecular Biology
Kazuhiro Kakimi, Takahiro Karasaki, Hirokazu Matsushita, Tomoharu Sugie
There are currently three major approaches to T cell-based cancer immunotherapy, namely, active vaccination, adoptive cell transfer therapy and immune checkpoint blockade. Recently, this latter approach has demonstrated remarkable clinical benefits, putting cancer immunotherapy under the spotlight. Better understanding of the dynamics of anti-tumor immune responses (the "Cancer-Immunity Cycle") is crucial for the further development of this form of treatment. Tumors employ multiple strategies to escape from anti-tumor immunity, some of which result from the selection of cancer cells with immunosuppressive activity by the process of cancer immunoediting...
March 21, 2016: Breast Cancer: the Journal of the Japanese Breast Cancer Society
Bernhard Mlecnik, Gabriela Bindea, Helen K Angell, Pauline Maby, Mihaela Angelova, David Tougeron, Sarah E Church, Lucie Lafontaine, Maria Fischer, Tessa Fredriksen, Maristella Sasso, Amélie M Bilocq, Amos Kirilovsky, Anna C Obenauf, Mohamad Hamieh, Anne Berger, Patrick Bruneval, Jean-Jacques Tuech, Jean-Christophe Sabourin, Florence Le Pessot, Jacques Mauillon, Arash Rafii, Pierre Laurent-Puig, Michael R Speicher, Zlatko Trajanoski, Pierre Michel, Richard Sesboüe, Thierry Frebourg, Franck Pagès, Viia Valge-Archer, Jean-Baptiste Latouche, Jérôme Galon
Microsatellite instability in colorectal cancer predicts favorable outcomes. However, the mechanistic relationship between microsatellite instability, tumor-infiltrating immune cells, Immunoscore, and their impact on patient survival remains to be elucidated. We found significant differences in mutational patterns, chromosomal instability, and gene expression that correlated with patient microsatellite instability status. A prominent immune gene expression was observed in microsatellite-instable (MSI) tumors, as well as in a subgroup of microsatellite-stable (MSS) tumors...
March 15, 2016: Immunity
Kari Hemminki, Kristina Sundquist, Jan Sundquist, Akseli Hemminki, Jianguang Ji
Cancer of unknown primary (CUP) is a fatal disease diagnosed through metastases. It shows intriguing familial clustering with certain defined primary cancers. Here we examine whether metastatic location in CUP patients is related to primary non-CUP cancers in relatives based on the Swedish Cancer Registry. Standardized incidence ratios (SIRs) were calculated for CUP patients defined by metastatic location depending on cancer in their first degree relatives. SIRs for CUP were high in association with liver (3...
2016: Scientific Reports
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