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https://www.readbyqxmd.com/read/29151021/regulatory-t-cells-induced-by-b-cells-a-novel-subpopulation-of-regulatory-t-cells
#1
REVIEW
Chien-Hui Chien, Bor-Luen Chiang
Regulatory T cells play a crucial role in the homeostasis of the immune response. In addition to CD4(+)Foxp3(+) regulatory T cells, several subsets of Foxp3(-) regulatory T cells, such as T helper 3 (Th3) cells and type 1 regulatory T (Tr1) cells, have been described in mice and human. Accumulating evidence shows that naïve B cells contribute to tolerance and are able to promote regulatory T cell differentiation. Naïve B cells can convert CD4(+)CD25(-) T cells into CD25(+)Foxp3(-) regulatory T cells, named Treg-of-B cells by our group...
November 18, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29147629/trial-watch-immune-checkpoint-blockers-for-cancer-therapy
#2
REVIEW
Claire Vanpouille-Box, Claire Lhuillier, Lucillia Bezu, Fernando Aranda, Takahiro Yamazaki, Oliver Kepp, Jitka Fucikova, Radek Spisek, Sandra Demaria, Silvia C Formenti, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi
Immune checkpoint blockers (ICBs) are literally revolutionizing the clinical management of an ever more diversified panel of oncological indications. Although considerable attention persists around the inhibition of cytotoxic T lymphocyte-associated protein 4 (CTLA4) and programmed cell death 1 (PDCD1, best known as PD-1) signaling, several other co-inhibitory T-cell receptors are being evaluated as potential targets for the development of novel ICBs. Moreover, substantial efforts are being devoted to the identification of biomarkers that reliably predict the likelihood of each patient to obtain clinical benefits from ICBs in the absence of severe toxicity...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29137877/immune-analysis-of-radium-223-in-patients-with-metastatic-prostate-cancer
#3
Joseph W Kim, Min Sun Shin, Youna Kang, Insoo Kang, Daniel P Petrylak
BACKGROUND: Radium223 (Ra223) delivers high-energy radiation to osteoblastic metastasis of prostate cancer, resulting in irreparable double-stranded DNA damage. The effects of Ra223 on CD8+ T cell subsets in patients with prostate cancer is unknown. PATIENTS AND METHODS: Fifteen men with metastatic prostate cancer with clinical indication for Ra223 without any autoimmune or immune deficiency conditions were enrolled. Patients received a course of Ra223 50 kBq/kg...
October 24, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29137331/hdac-inhibitors-enhance-the-immunotherapy-response-of-melanoma-cells
#4
Laurence Booth, Jane L Roberts, Andrew Poklepovic, John Kirkwood, Paul Dent
We focused on the ability of the pan-histone deacetylase (HDAC) inhibitors AR42 and sodium valproate to alter the immunogenicity of melanoma cells. Treatment of melanoma cells with HDAC inhibitors rapidly reduced the expression of multiple HDAC proteins as well as the levels of PD-L1, PD-L2 and ODC, and increased expression of MHCA. In a cell-specific fashion, melanoma isolates released the immunogenic protein HMGB1 into the extracellular environment. Very similar data were obtained in ovarian and H&NSCC PDX isolates, and in established tumor cell lines from the lung and kidney...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29133939/precision-medicine-for-urothelial-bladder-cancer-update-on-tumour-genomics-and-immunotherapy
#5
REVIEW
Kenneth M Felsenstein, Dan Theodorescu
Effective management of advanced urothelial bladder cancer is challenging. New discoveries that improve our understanding of molecular bladder cancer subtypes have revealed numerous potentially targetable genomic alterations and demonstrated the efficacy of treatments that harness the immune system. These findings have begun to change paradigms of bladder cancer therapy. For example, DNA repair pathway mutations in genes such as ERCC2, FANCC, ATM, RB1, and others can predict responses to neoadjuvant platinum-based chemotherapies and to targeted therapies on the basis of mutation status...
November 14, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/29130827/association-of-single-nucleotide-polymorphisms-in-immune-related-genes-with-development-of-dengue-hemorrhagic-fever-in-a-mexican-population
#6
Angélica Berenice Vargas-Castillo, Karina Ruiz-Tovar, Héctor Vivanco-Cid, Sarai Quiroz-Cruz, Alejandro Escobar-Gutiérrez, Jorge Francisco Cerna-Cortes, Gilberto Vaughan, Salvador Fonseca-Coronado
Single-nucleotide polymorphisms (SNPs) occurring in immune-related genes have been associated with risk or protection for development of dengue, depending on ethnicity. Here, we genotyped seven SNPs located in immune response-related genes to identify their association with severe forms of dengue in patients from an endemic region in Mexico. One hundred and thirty-eight patients with dengue fever (DF), thirty-one dengue hemorrhagic fever (DHF) patients, as well as 304 healthy donors were genotyped by using a TaqMan-based approach...
November 13, 2017: Viral Immunology
https://www.readbyqxmd.com/read/29125731/imaging-pd-l1-expression-with-immunopet
#7
Charles Truillet, Hsueh Ling J Oh, Siok Ping Yeo, Chia-Yin Lee, Loc T Huynh, Junnian Wei, Matthew F L Parker, Collin Blakely, Natalia Sevillano, Yung-Hua Wang, Yuqin S Shen, Victor Olivas, Khaled M Jami, Anna Moroz, Benoit Jego, Emilie Jaumain, Lawrence Fong, Charles S Craik, Albert J Chang, Trever G Bivona, Cheng-I Wang, Michael J Evans
High sensitivity imaging tools could provide a more holistic view of target antigen expression to improve the identification of patients who might benefit from cancer immunotherapy. We developed for immunoPET a novel recombinant human IgG1 (termed C4) that potently binds an extracellular epitope on human and mouse PD-L1 and radiolabeled the antibody with zirconium-89. Small animal PET/CT studies showed that (89)Zr-C4 detected antigen levels on a patient derived xenograft (PDX) established from a non-small-cell lung cancer (NSCLC) patient before an 8-month response to anti-PD-1 and anti-CTLA4 therapy...
November 15, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29120224/is-there-a-role-for-programmed-death-ligand-1-testing-and-immunotherapy-in-colorectal-cancer-with-microsatellite-instability-part-ii-the-challenge-of-programmed-death-ligand-1-testing-and-its-role-in-microsatellite-instability-high-colorectal-cancer
#8
Esmeralda Celia Marginean, Barbara Melosky
CONTEXT: - The world of oncology has changed dramatically in the past few years with the introduction of checkpoint inhibitors and immunotherapy. The promising findings of a small, phase 2 clinical trial that led to the US Food and Drug Administration breakthrough designation and approval of the anti-programmed death receptor-1 (PD-1) drug pembrolizumab (Keytruda, Merck, Kenilworth, New Jersey) to treat metastatic/refractory microsatellite instability-high colorectal cancer (CRC) has significantly boosted interest in immunomodulatory therapies in microsatellite instability-high CRC...
November 9, 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/29118259/matrix-binding-checkpoint-immunotherapies-enhance-antitumor-efficacy-and-reduce-adverse-events
#9
Jun Ishihara, Kazuto Fukunaga, Ako Ishihara, Hans M Larsson, Lambert Potin, Peyman Hosseinchi, Gabriele Galliverti, Melody A Swartz, Jeffrey A Hubbell
Immune checkpoint blockade exhibits considerable antitumor activity, but previous studies have reported instances of severe treatment-related adverse events. We sought to explore local immune checkpoint blockade, with an antibody (Ab) form that would be retained intra- or peritumorally, limiting systemic exposure. To accomplish this, we conjugated the checkpoint blockade Abs to an extracellular matrix (ECM)-super-affinity peptide derived from placenta growth factor-2 (PlGF-2123-144). We show enhanced tissue retention and lower Ab concentrations in blood plasma after PlGF-2123-144 conjugation, reducing systemic side effects such as the risk of autoimmune diabetes...
November 8, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29113654/the-role-of-intestinal-bacteria-in-the-development-and-progression-of-gastrointestinal-tract-neoplasms
#10
REVIEW
Kosuke Mima, Shuji Ogino, Shigeki Nakagawa, Hiroshi Sawayama, Koichi Kinoshita, Ryuichi Krashima, Takatsugu Ishimoto, Katsunori Imai, Masaaki Iwatsuki, Daisuke Hashimoto, Yoshifumi Baba, Yasuo Sakamoto, Yo-Ichi Yamashita, Naoya Yoshida, Akira Chikamoto, Takatoshi Ishiko, Hideo Baba
More than 100 trillion microorganisms inhabit the human intestinal tract and play important roles in health conditions and diseases, including cancer. Accumulating evidence demonstrates that specific bacteria and bacterial dysbiosis in the gastrointestinal tract can potentiate the development and progression of gastrointestinal tract neoplasms by damaging DNA, activating oncogenic signaling pathways, producing tumor-promoting metabolites such as secondary bile acids, and suppressing antitumor immunity. Other bacterial species have been shown to produce short-chain fatty acids such as butyrate, which can suppress inflammation and carcinogenesis in the gastrointestinal tract...
December 2017: Surgical Oncology
https://www.readbyqxmd.com/read/29109092/screening-for-multiple-autoantibodies-in-plasma-of-patients-with-breast-cancer
#11
REVIEW
Lauren Bassaro, Stephen J Russell, Elzbieta Pastwa, Stella A Somiari, Richard I Somiari
BACKGROUND/AIM: Autoantibodies have potential as circulating biomarkers for early cancer detection. This study aimed to screen for known autoantibodies in human plasma using an Autoantibody Profiling System (APS) and quantify the levels in plasma of donors with/without breast cancer. MATERIALS AND METHODS: Plasma from nine female donors diagnosed with breast cancer (test group) and nine matched donors with no personal history of cancer (reference group) were screened with an APS containing probes for 30 autoantibodies...
November 2017: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/29096669/anti-carbamylated-protein-antibodies-precede-disease-onset-in-monkeys-with-collagen-induced-arthritis
#12
Marije K Verheul, Michel P M Vierboom, Bert A 't Hart, Rene E M Toes, Leendert A Trouw
BACKGROUND: Rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA) and anti-carbamylated protein (anti-CarP) antibodies are rheumatoid arthritis (RA)-associated autoantibodies. Besides their presence in human serum, anti-CarP antibodies have also been described in rodent models of arthritis, while ACPA are not consistently detectable. Data on these RA-associated autoantibodies in primates are not available. Therefore, we investigated the presence of RF, anti-CarP antibodies and ACPA in rhesus monkeys before and after collagen-induced arthritis immunizations...
November 2, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29090224/production-and-evaluation-of-specific-single-chain-antibodies-against-ctla-4-for-cancer-targeted-therapy
#13
Farideh Hosseinzadeh, Saeed Mohammadi, Foroogh Nejatollahi
BACKGROUND: Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) molecules are expressed on T-cells and inhibit their function by inhibiting activation of subsequent T-cell molecular pathways. Blocking of CTLA-4 inhibits the growth of malignant tumor cells. Anti-CTLA-4 monoclonal antibodies activate the immune system against cancer. Due to several advantages of single-chain antibodies (scFvs) compared to monoclonal antibodies in cancer immunotherapy, specific anti-CTLA-4 scFvs (single-chain variable fragment) were selected in this study...
October 2017: Reports of Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/29079801/development-of-a-curative-therapeutic-vaccine-theravac-for-the-treatment-of-large-established-tumors
#14
Yingjie Nie, De Yang, Anna Trivett, Zhen Han, Haiyun Xin, Xin Chen, Joost J Oppenheim
Harnessing immune system to treat cancer requires simultaneous generation of tumor-specific CTLs and curtailment of tumor immunosuppressive environment. Here, we developed an immunotherapeutic regimen capable of eliminating large established mouse tumors using HMGN1, a DC-activating TLR4 agonist capable of inducing anti-tumor immunity. Intratumoral delivery of HMGN1 with low dose of Cytoxan cured mice bearing small (∅ ≈ 0.5 cm), but not large (∅ ≈ 1.0 cm) CT26 tumors. Screening for activators capable of synergizing with HMGN1 in activating DC identified R848...
October 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29070816/resistance-to-checkpoint-blockade-therapy-through-inactivation-of-antigen-presentation
#15
Moshe Sade-Feldman, Yunxin J Jiao, Jonathan H Chen, Michael S Rooney, Michal Barzily-Rokni, Jean-Pierre Eliane, Stacey L Bjorgaard, Marc R Hammond, Hans Vitzthum, Shauna M Blackmon, Dennie T Frederick, Mehlika Hazar-Rethinam, Brandon A Nadres, Emily E Van Seventer, Sachet A Shukla, Keren Yizhak, John P Ray, Daniel Rosebrock, Dimitri Livitz, Viktor Adalsteinsson, Gad Getz, Lyn M Duncan, Bo Li, Ryan B Corcoran, Donald P Lawrence, Anat Stemmer-Rachamimov, Genevieve M Boland, Dan A Landau, Keith T Flaherty, Ryan J Sullivan, Nir Hacohen
Treatment with immune checkpoint blockade (CPB) therapies often leads to prolonged responses in patients with metastatic melanoma, but the common mechanisms of primary and acquired resistance to these agents remain incompletely characterized and have yet to be validated in large cohorts. By analyzing longitudinal tumor biopsies from 17 metastatic melanoma patients treated with CPB therapies, we observed point mutations, deletions or loss of heterozygosity (LOH) in beta-2-microglobulin (B2M), an essential component of MHC class I antigen presentation, in 29...
October 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/29069245/belatacept-in-kidney-transplantation-past-and-future-perspectives
#16
Zaki Siddiqui, Hélio Tedesco-Silva, Leonardo V Riella
Calcineurin inhibitors (CNIs) are used widely for maintenance immunosuppression in renal transplant recipients. However, their side effect profile has led researchers to attempt to find safer alternatives that can maintain effective long-term immunosuppression with less toxicity. Belatacept is a CTLA4-Ig molecule designed to block the costimulatory B7-CD28 signal needed for activation of effector T cells. While it has shown great promise in clinical trials, it has made halting progress towards replacing CNIs in actual clinical practice...
April 2017: Jornal Brasileiro de Nefrologia: ʹorgão Oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
https://www.readbyqxmd.com/read/29066174/attenuation-of-cd4-cd25-regulatory-t-cells-in-the-tumor-microenvironment-by-metformin-a-type-2-diabetes-drug
#17
Yuki Kunisada, Shingo Eikawa, Nahoko Tomonobu, Shohei Domae, Takenori Uehara, Shohei Hori, Yukihiro Furusawa, Koji Hase, Akira Sasaki, Heiichiro Udono
CD4(+)CD25(+) regulatory T cells (Treg), an essential subset for preventing autoimmune diseases, is implicated as a negative regulator in anti-tumor immunity. We found that metformin (Met) reduced tumor-infiltrating Treg (Ti-Treg), particularly the terminally-differentiated CD103(+)KLRG1(+) population, and also decreased effector molecules such as CTLA4 and IL-10. Met inhibits the differentiation of naïve CD4(+) T cells into inducible Treg (iTreg) by reducing forkhead box P3 (Foxp3) protein, caused by mTORC1 activation that was determined by the elevation of phosphorylated S6 (pS6), a downstream molecule of mTORC1...
October 16, 2017: EBioMedicine
https://www.readbyqxmd.com/read/29059149/targeting-immunosuppressive-adenosine-in-cancer
#18
REVIEW
Dipti Vijayan, Arabella Young, Michele W L Teng, Mark J Smyth
Despite the success of anti-programmed cell death protein 1 (PD1), anti-PD1 ligand 1 (PDL1) and anti-cytotoxic T lymphocyte antigen 4 (CTLA4) therapies in advanced cancer, a considerable proportion of patients remain unresponsive to these treatments (known as innate resistance). In addition, one-third of patients relapse after initial response (known as adaptive resistance), which suggests that multiple non-redundant immunosuppressive mechanisms coexist within the tumour microenvironment. A major immunosuppressive mechanism is the adenosinergic pathway, which now represents an attractive new therapeutic target for cancer therapy...
October 23, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29047105/%C3%AE-secretase-inhibitor-reduces-immunosuppressive-cells-and-enhances-tumour-immunity-in-head-and-neck-squamous-cell-carcinoma
#19
Liang Mao, Zhi-Li Zhao, Guang-Tao Yu, Lei Wu, Wei-Wei Deng, Yi-Cun Li, Jian-Feng Liu, Lin-Lin Bu, Bing Liu, Ashok B Kulkarni, Wen-Feng Zhang, Lu Zhang, Zhi-Jun Sun
Immune evasion is a hallmark feature of cancer, and it plays an important role in tumour initiation and progression. In addition, tumour immune evasion severely hampers the desired antitumour effect in multiple cancers. In this study, we aimed to investigate the role of the Notch pathway in immune evasion in the head and neck squamous cell carcinoma (HNSCC) microenvironment. We first demonstrated that Notch1 signalling was activated in a Tgfbr1/Pten-knockout HNSCC mouse model. Notch signalling inhibition using a γ-secretase inhibitor (GSI-IX, DAPT) decreased tumour burden in the mouse model after prophylactic treatment...
October 19, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29046101/anorectal-melanoma-experience-from-a-tertiary-cancer-care-centre-in-south-india
#20
S Ranjith, M Muralee, A Sajeed, P M Arun, K Cherian, C K Nair, P Augustine, I Ahamed
Introduction Mucosal malignant melanoma of the anorectum is a rare and aggressive disease, in which early diagnosis is difficult. The prognosis remains extremely poor, irrespective of the treatment. We share our experience in treating this malignancy at our centre in South India. Methods This study describes a retrospective analysis of 31 cases of anorectal melanoma presented to our centre between January 2001 and December 2013. Results Twenty-two patients (71%) presented with metastasis and had a median overall survival of nine months...
October 19, 2017: Annals of the Royal College of Surgeons of England
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