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Cancer immunology

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https://www.readbyqxmd.com/read/28214182/opportunistic-autoimmunity-secondary-to-cancer-immunotherapy-oasi-an-emerging-challenge
#1
M Kostine, L Chiche, E Lazaro, P Halfon, C Charpin, D Arniaud, F Retornaz, P Blanco, N Jourde-Chiche, C Richez, C Stavris
With "checkpoint inhibitors" targeting PD1/PD-1-ligands or CTLA-4/CD28 pathways, immunotherapy has profoundly modified therapeutic strategies in oncology. First approved in refractory metastatic neoplasms (melanoma and lung adenocarcinoma), it is now being tested broadly in other cancers and/or as adjuvant treatment. For a significant proportion of patients, immunotherapy is responsible for "immunological" events, identified as Immune-Related Adverse Events (irAEs). Owing to the increasing number of prescriptions, identification and management of specific immunological side effects is crucial and requires close collaboration between oncologists and internists and/or other organ specialists...
February 14, 2017: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/28210393/has-vitamin-d-had-its-time-in-the-sun-for-melanoma
#2
Christopher J Huerter, Adam Vaudreuil, Devendra K Agrawal, Austin Huy Nguyen
Growing evidence suggests a pivotal role for vitamin D in cancers, particularly melanoma. The broad immunologic effects of vitamin D and its signaling axis make for a complex interplay between tumor cells and the immune system. Preclinical evidence suggests vitamin D to have protective effects in melanoma oncogenesis and progression, creating a potential role for vitamin D supplementation in cancer prevention and/or adjuvant therapy. In this commentary, the authors highlight studies of vitamin D in melanoma with clinical implications and call for large clinical trials to definitively determine the role of supplementation in patients to prevent and help treat melanoma...
December 2016: Journal of Clinical and Aesthetic Dermatology
https://www.readbyqxmd.com/read/28209609/pancreatic-cancer-progress-and-challenges-in-a-rapidly-moving-field
#3
Eric A Collisson, Kenneth P Olive
"Pancreatic Cancer: Advances in Science and Clinical Care," a Special Conference of the American Association for Cancer Research, was held in Orlando, FL, on May 12 to 15, bringing together more than 450 basic, translational, clinical, and epidemiologic pancreatic cancer researchers as well as pancreatic cancer patients, survivors, and advocates. Pancreatic cancer remains one of the great challenges in medicine, but the accelerating pace of research and early hints of clinical successes to come were palpable throughout the meeting...
February 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28205652/bridging-the-gap-microfluidic-devices-for-short-and-long-distance-cell-cell-communication
#4
REVIEW
Timothy Quang Vu, Ricardo Miguel Bessa de Castro, Lidong Qin
Cell-cell communication is a crucial component of many biological functions. For example, understanding how immune cells and cancer cells interact, both at the immunological synapse and through cytokine secretion, can help us understand and improve cancer immunotherapy. The study of how cells communicate and form synaptic connections is important in neuroscience, ophthalmology, and cancer research. But in order to increase our understanding of these cellular phenomena, better tools need to be developed that allow us to study cell-cell communication in a highly controlled manner...
February 16, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28202613/the-activating-human-nk-cell-receptor-kir2ds2-recognizes-a-%C3%AE-2-microglobulin-independent-ligand-on-cancer-cells
#5
Lavanya Thiruchelvam-Kyle, Sigurd E Hoelsbrekken, Per C Saether, Elisabeth Gyllensten Bjørnsen, Daniela Pende, Sigbjørn Fossum, Michael R Daws, Erik Dissen
The functions of activating members of the killer cell Ig-like receptor (KIR) family are not fully understood, as the ligands for these receptors are largely unidentified. In this study, we report that KIR2DS2 reporter cells recognize a ligand expressed by cancer cell lines. All cancer targets recognized by KIR2DS2 were also recognized by KIR2DL2 and KIR2DL3 reporters. Trogocytosis of membrane proteins from the cancer targets was observed with responding reporter cells, indicating the formation of KIR2DS2 ligand-specific immunological synapses...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28201977/targeting-the-immune-niche-within-the-bone-marrow-microenvironment-the-rise-of-immunotherapy-in-multiple-myeloma
#6
Klaus Podar, D Jäger
Multiple Myeloma (MM) cells inhibit the development of an effective anti-MM immune response via defects in T cell function, ineffective antigen presentation; reduced phagocytic capacity; natural killer and dendritic cell dysfunction; decreased responsiveness to IL-2 and defects in B cell immunity; upregulation of inhibitory pathways; and production of excessive pro-inflammatory cytokines. Moreover, immune cells including plasmacytoid dendritic cells and macrophages trigger tumor cell proliferation, survival, and drug resistance...
February 13, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28199204/the-crossroads-between-cancer-immunity-and-autoimmunity-antibodies-to-self-antigens
#7
Monica Benvenuto, Rosanna Mattera, Laura Masuelli, Ilaria Tresoldi, Maria Gabriella Giganti, Giovanni Vanni Frajese, Vittorio Manzari, Andrea Modesti, Roberto Bei
The production of autoantibodies to self antigens is dependent on the failure of immune tolerance. Cancer cells express antigens which elicit a spontaneous immune response in cancer patients. The repertoire of autoantibodies found in cancer patients partly covers that of patients with autoimmune diseases. Biological activities of autoantibodies to self antigens may induce paraneoplastic syndromes which reflect the attempt of cancer patients to counteract tumor growth. Autoantibodies with similar specificities may have different effects in cancer and autoimmune disease patients due to different immunological microenvironments...
March 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28198830/-final-common-pathway-of-human-cancer-immunotherapy-targeting-random-somatic-mutations
#8
REVIEW
Eric Tran, Paul F Robbins, Steven A Rosenberg
Effective clinical cancer immunotherapies, such as administration of the cytokine IL-2, adoptive cell transfer (ACT) and the recent success of blockade of the checkpoint modulators CTLA-4 and PD-1, have been developed without clear identification of the immunogenic targets expressed by human cancers in vivo. Immunotherapy of patients with cancer through the use of ACT with autologous lymphocytes has provided an opportunity to directly investigate the antigen recognition of lymphocytes that mediate cancer regression in humans...
February 15, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28198364/interleukin-22-drives-nitric-oxide-dependent-dna-damage-and-dysplasia-in-a-murine-model-of-colitis-associated-cancer
#9
C Wang, G Gong, A Sheh, S Muthupalani, E M Bryant, D A Puglisi, H Holcombe, E A Conaway, N A P Parry, V Bakthavatchalu, S P Short, C S Williams, G N Wogan, S R Tannenbaum, J G Fox, B H Horwitz
The risk of colon cancer is increased in patients with Crohn's disease and ulcerative colitis. Inflammation-induced DNA damage could be an important link between inflammation and cancer, although the pathways that link inflammation and DNA damage are incompletely defined. RAG2-deficient mice infected with Helicobacter hepaticus (Hh) develop colitis that progresses to lower bowel cancer. This process depends on nitric oxide (NO), a molecule with known mutagenic potential. We have previously hypothesized that production of NO by macrophages could be essential for Hh-driven carcinogenesis, however, whether Hh infection induces DNA damage in this model and whether this depends on NO has not been determined...
February 15, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28197385/prognostic-and-predictive-aspects-of-the-tumor-immune-microenvironment-and-immune-checkpoints-in-malignant-pleural-mesothelioma
#10
Elly Marcq, Vasiliki Siozopoulou, Jorrit De Waele, Jonas van Audenaerde, Karen Zwaenepoel, Eva Santermans, Niel Hens, Patrick Pauwels, Jan P van Meerbeeck, Evelien L J Smits
Malignant pleural mesothelioma (MPM) is an aggressive cancer with a poor prognosis and an increasing incidence, for which novel therapeutic strategies are urgently required. Since the immune system has been described to play a presumed role in the protection against MPM, characterization of its tumor immune microenvironment (TME) and immune checkpoints can identify new immunotherapeutic targets and their predictive and/or prognostic value. To characterize the TME and the immune checkpoint expression profile, we performed immunohistochemistry (IHC) on formalin-fixed paraffin embedded (FFPE) tissue sections from 54 MPM patients (40 at time of diagnosis; 14 treated with chemotherapy)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28197381/immunological-mechanisms-of-intravesical-chitosan-interleukin-12-immunotherapy-against-murine-bladder-cancer
#11
Sean G Smith, John L Baltz, Bhanu Prasanth Koppolu, Sruthi Ravindranathan, Khue Nguyen, David A Zaharoff
There is a critical unmet clinical need for bladder cancer immunotherapies capable of inducing durable antitumor immunity. We have shown that four intravesical treatments with a simple co-formulation of interleukin-12 and the biopolymer chitosan not only destroy orthotopic bladder tumors, but also promote a potent long-lasting systemic immune response as evidenced through tumor-specific in vitro killing assays, complete protection from rechallenge, and abscopal antitumor responses at distant non-treated tumors...
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
#12
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
https://www.readbyqxmd.com/read/28194445/diverse-repetitive-element-rna-expression-defines-epigenetic-and-immunologic-features-of-colon-cancer
#13
Niyati Desai, Dipti Sajed, Kshitij S Arora, Alexander Solovyov, Mihir Rajurkar, Jacob R Bledsoe, Srinjoy Sil, Ramzi Amri, Eric Tai, Olivia C MacKenzie, Mari Mino-Kenudson, Martin J Aryee, Cristina R Ferrone, David L Berger, Miguel N Rivera, Benjamin D Greenbaum, Vikram Deshpande, David T Ting
There is tremendous excitement for the potential of epigenetic therapies in cancer, but the ability to predict and monitor response to these drugs remains elusive. This is in part due to the inability to differentiate the direct cytotoxic and the immunomodulatory effects of these drugs. The DNA-hypomethylating agent 5-azacitidine (AZA) has shown these distinct effects in colon cancer and appears to be linked to the derepression of repeat RNAs. LINE and HERV are two of the largest classes of repeats in the genome, and despite many commonalities, we found that there is heterogeneity in behavior among repeat subtypes...
February 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28194024/regnase-1-a-rapid-response-ribonuclease-regulating-inflammation-and-stress-responses
#14
REVIEW
Renfang Mao, Riyun Yang, Xia Chen, Edward W Harhaj, Xiaoying Wang, Yihui Fan
RNA-binding proteins (RBPs) are central players in post-transcriptional regulation and immune homeostasis. The ribonuclease and RBP Regnase-1 exerts critical roles in both immune cells and non-immune cells. Its expression is rapidly induced under diverse conditions including microbial infections, treatment with inflammatory cytokines and chemical or mechanical stimulation. Regnase-1 activation is transient and is subject to negative feedback mechanisms including proteasome-mediated degradation or mucosa-associated lymphoid tissue 1 (MALT1) mediated cleavage...
February 13, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28194021/type-i-ifn-augments-il-27-dependent-trim25-expression-to-inhibit-hbv-replication
#15
Guangyun Tan, Qingfei Xiao, Hongxiao Song, Feng Ma, Fengchao Xu, Di Peng, Na Li, Xiaosong Wang, Junqi Niu, Pujun Gao, F Xiao-Feng Qin, Genhong Cheng
Hepatitis B virus (HBV) can cause chronic hepatitis B, which may lead to cirrhosis and liver cancer. Type I interferon (IFN) is an approved drug for the treatment of chronic hepatitis B. However, the fundamental mechanisms of antiviral action by type I IFN and the downstream signaling pathway are unclear. TRIM25 is an IFN-stimulated gene (ISG) that has an important role in RIG-I ubiquitination and activation. Whether TRIM25 is induced in liver cells by type I IFN to mediate anti-HBV function remains unclear...
February 13, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28188495/cancer-treatment-and-the-kir-hla-system-an-overview
#16
REVIEW
Patrizia Leone, Valli De Re, Angelo Vacca, Franco Dammacco, Vito Racanelli
Accumulating evidence indicates that the success of cancer therapy depends not only on a combination of adequate procedures (surgery, chemotherapy and radiotherapy) that aim to eliminate all tumor cells, but also on the functional state of the host immune system. HLA and KIR molecules, in particular, are critical to the interactions between tumor cells and both innate and adaptive immune cells such as NK cells and T cells. Different KIR-HLA gene combinations as well as different HLA expression levels on tumor cells associate with variable tumor prognosis and response to treatment...
February 10, 2017: Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/28181678/safety-and-immunological-efficacy-of-a-dna-vaccine-encoding-the-androgen-receptor-ligand-binding-domain-ar-lbd
#17
Brian M Olson, Eric S Bradley, Thomas Sawicki, Weixiong Zhong, Erik A Ranheim, Jordan E Bloom, Viswa T Colluru, Laura E Johnson, Brian T Rekoske, Jens C Eickhoff, Douglas G McNeel
BACKGROUND: The androgen receptor (AR) is a key oncogenic driver of prostate cancer, and has been the primary focus of prostate cancer treatment for several decades. We have previously demonstrated that the AR is also an immunological target antigen, recognized in patients with prostate cancer, and targetable by means of vaccines in rodent models with delays in prostate tumor growth. The current study was performed to determine the safety and immunological efficacy of a GMP-grade plasmid DNA vaccine encoding the ligand-binding domain (LBD) of the AR, pTVG-AR...
February 9, 2017: Prostate
https://www.readbyqxmd.com/read/28178711/experimental-treatments-for-leptomeningeal-metastases-from-solid-malignancies
#18
Solmaz Sahebjam, Peter A Forsyth, Keiran S Smalley, Nam D Tran
BACKGROUND: Leptomeningeal metastasis is a consequence of advanced solid malignancies and has limited treatment options. It is possible that it is becoming more common as the leptomeninges act as a sanctuary site for recurrence from systemic cancer. METHODS: Potential targeted and immunotherapy agents for the most common types of solid-tumor leptomeningeal metastasis are reviewed, as are their dosing/delivery strategies and novel, immunological approaches. RESULTS: Historically, patients with leptomeningeal metastasis have been excluded from clinical trials, and data on the management of leptomeningeal metastasis come from single case reports and retrospective analyses...
January 2017: Cancer Control: Journal of the Moffitt Cancer Center
https://www.readbyqxmd.com/read/28178396/immunological-evaluation-of-peptide-vaccination-for-cancer-patients-with-the-hla-a11-or-a33-allele
#19
Shijoro Sakamoto, Satoko Matsueda, Shinzou Takamori, Uhi Toh, Masanori Noguchi, Shigeru Yutani, Akira Yamada, Shigeki Shichijo, Teppei Yamada, Shigetaka Suekane, Kouichirou Kawano, Masayasu Naitou, Tetsuro Sasada, Noboru Hattori, Nobuoki Kohno, Kyogo Itoh
The HLA-A11 or -A33 allele is found in approximately 18% or 10% of the Asian population, respectively, but each of which is a minor allele worldwide, and therefore no clinical trials were previously conducted. To develop a therapeutic peptide vaccine for each of them, we investigated immunological responses of advanced cancer patients with the HLA-A11(+) /A11(+) (n=18) or -A33(+) /A33(+) (n=13) allele to personalized peptide vaccine (PPV) regimens. The primary sites of HLA-A11+/A11+ or -A33+/A33+ patients were the colon (n=4 or 2), stomach (2 or 3), breast (3 or 2), lung and pancreas(2 or 2), and so on...
February 8, 2017: Cancer Science
https://www.readbyqxmd.com/read/28178038/p-selectin-glycoprotein-ligand-1-in-t-cells
#20
Michael Abadier, Klaus Ley
PURPOSE OF REVIEW: We review P-selectin glycoprotein ligand-1 (PSGL-1) as a selectin and chemokine-binding adhesion molecule. PSGL-1 is widely studied in neutrophils. Here, we focus on T cells, because PSGL-1 was recently described as a major immunomodulatory molecule during viral infection. PSGL-1 also plays a crucial role in T-cell homeostasis by binding to lymphoid chemokines, and can induce tolerance by enhancing the functions of regulatory T cells. RECENT FINDINGS: PSGL-1 was originally described as a leukocyte ligand for P-selectin, but it is actually a ligand for all selectins (P-, L- and E-selectin), binds chemokines, activates integrins and profoundly affects T-cell biology...
February 7, 2017: Current Opinion in Hematology
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