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Immune check point

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https://www.readbyqxmd.com/read/29026068/hollow-mno2-as-a-tumor-microenvironment-responsive-biodegradable-nano-platform-for-combination-therapy-favoring-antitumor-immune-responses
#1
Guangbao Yang, Ligeng Xu, Yu Chao, Jun Xu, Xiaoqi Sun, Yifan Wu, Rui Peng, Zhuang Liu
Herein, an intelligent biodegradable hollow manganese dioxide (H-MnO2) nano-platform is developed for not only tumor microenvironment (TME)-specific imaging and on-demand drug release, but also modulation of hypoxic TME to enhance cancer therapy, resulting in comprehensive effects favoring anti-tumor immune responses. With hollow structures, H-MnO2 nanoshells post modification with polyethylene glycol (PEG) could be co-loaded with a photodynamic agent chlorine e6 (Ce6), and a chemotherapy drug doxorubicin (DOX)...
October 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28984923/b-cell-tolerance-to-epidermal-ribonuclear-associated-neo-autoantigen-in-vivo
#2
Søren E Degn, Elisabeth Alicot, Michael C Carroll
Defining how self-antigens are perceived by the immune system is pivotal to understand how tolerance is maintained under homeostatic conditions. Clinically relevant, natural autoantigens targeted by autoantibodies in e.g. systemic lupus erythematosus (SLE) commonly have an intrinsic ability to engage not only the B cell receptor (BCR), but also a costimulatory pathway in B cells, such as the TLR7 pathway. Here we developed a novel mouse model displaying inducible expression of a fluorescent epidermal neo-autoantigen carrying an OT-II T cell epitope, B cell antigen, and associated ribonucleic acids capable of stimulating TLR7...
October 6, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28975380/immunological-classification-of-renal-cell-carcinoma-patients-based-on-phenotypic-analysis-of-immune-check-point-molecules
#3
Atsunari Kawashima, Takayuki Kanazawa, Kumiko Goto, Mitsunobu Matsumoto, Akiko Morimoto-Okazawa, Kota Iwahori, Takeshi Ujike, Akira Nagahara, Kazutoshi Fujita, Motohide Uemura, Norio Nonomura, Hisashi Wada
OBJECTIVES: To clarify comprehensive immunological signature patterns of tumour tissue-infiltrating lymphocytes in patients with renal cell carcinoma and show its clinical significance. MATERIALS AND METHODS: We investigated the surface marker expressions of tumour tissue-infiltrating lymphocytes quantitatively and classified them based on their functional populations. We extracted 109 sets of tumour tissue-infiltrating lymphocytes from 80 patients who underwent surgical resection of renal cell carcinoma, of which 44 tumour tissue-infiltrating lymphocytes were multiply extracted from 15 patients...
October 3, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28971752/response-of-advanced-stage-recurrent-lymphoepithelioma-like-carcinoma-to-nivolumab
#4
Vivek Kumar, Vishangi Dave, Jonathan Harris, Yiwu Huang
Lymphoepithelioma-like carcinoma (LELC) of lung is a rare tumor that is mostly reported in south-east Asian countries. The surgical removal is curative in the early stages but there is no consensus on the choice of chemotherapy for the treatment of advanced stage tumors. Most of the data on chemotherapy are based on small case series and retrospective studies. As per available data, this tumor responds to chemotherapy initially but recurrences are common. The use of conventional chemotherapy in recurrent tumors leads to cumulative toxicities in the long term...
September 2017: Immunotherapy
https://www.readbyqxmd.com/read/28929192/role-of-pd-1-in-immunity-and-diseases
#5
Kenji Chamoto, Muna Al-Habsi, Tasuku Honjo
Immunity developed to defend our bodies from foreign particles, including bacteria and viruses. Although effector cells responsible for acquired immunity, mainly T cells, and B cells, are able to distinguish self from non-self, they sometimes attack the body's tissues because of imperfect central tolerance. Several immune check points developed to limit overactivation of these cells. One of the most important immune checkpoints is programmed cell death-1 (PD-1), which is expressed mainly on activated lymphocytes...
September 20, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28878676/pd-1-and-pd-l1-checkpoint-signaling-inhibition-for-cancer-immunotherapy-mechanism-combinations-and-clinical-outcome
#6
REVIEW
Hashem O Alsaab, Samaresh Sau, Rami Alzhrani, Katyayani Tatiparti, Ketki Bhise, Sushil K Kashaw, Arun K Iyer
Several cancers are highly refractory to conventional chemotherapy. The survival of tumors in several cases is assisted by checkpoint immunomodulation to maintain the imbalance between immune surveillance and cancer cell proliferation. Check point antibody inhibitors, such as anti-PD-1/PD-L1, are a novel class of inhibitors that function as a tumor suppressing factor via modulation of immune cell-tumor cell interaction. These checkpoint blockers are rapidly becoming a highly promising cancer therapeutic approach that yields remarkable antitumor responses with limited side effects...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28865357/check-point-inhibitors-as-therapies-for-infectious-diseases
#7
REVIEW
Maureen A Cox, Robert Nechanitzky, Tak W Mak
The recent successes of immune check point targeting therapies in treating cancer patients has driven a resurgence of interest in targeting these pathways in chronically infected patients. While still in early stages, basic and clinical data suggest that blockade of CTLA-4 and PD-1 can be beneficial in the treatment of chronic HIV, HBV, and HCV infection, as well as other chronic maladies. Furthermore, novel inhibitory receptors such as Tim-3, LAG-3, and TIGIT are the potential next wave of check points that can be manipulated for the treatment of chronic infection...
August 30, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28844952/targeting-cholangiocarcinoma
#8
REVIEW
Joachim C Mertens, Sumera Rizvi, Gregory J Gores
Cholangiocarcinoma (CCA) represents a diverse group of epithelial cancers associated with the biliary tract, and can best be stratified anatomically into intrahepatic (iCCA), perihilar (pCCA) and distal (dCCA) subsets. Molecular profiling has identified genetic aberrations associated with these anatomic subsets. For example, IDH catalytic site mutations and constitutively active FGFR2 fusion genes are predominantly identified in iCCA, whereas KRAS mutations and PRKACB fusions genes are identified in pCCA and dCCA...
August 24, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28843709/pd-l1-in-breast-cancer-comparative-analysis-of-three-different-antibodies
#9
Tejashree Karnik, Bruce F Kimler, Fang Fan, Ossama Tawfik
The Programmed cell death-1 and its ligand-1 (PD-L1) interaction serve as a regulatory check against excessive immune response to antigen and autoimmunity. We compared the performance of three different PD-L1 antibodies (Ventana SP263, Dako 22C3 and BioCare RbMCAL10 antibodies) in 136 invasive ductal carcinoma specimens including 43 primary, 48 locally metastatic and 46 distantly metastatic disease. PD-L1 expression was correlated with clinicopathologic parameters including tumor size, grade, lymphovascular invasion, estrogen receptor (ER), progesterone receptor (PgR), HER2, Ki67, molecular type, TN status...
August 23, 2017: Human Pathology
https://www.readbyqxmd.com/read/28823141/targeted-therapy-of-ovarian-cancer-including-immune-check-point-inhibitor
#10
REVIEW
Jin Young Kim, Chi Heum Cho, Hong Suk Song
Epithelial ovarian cancer is the eighth most common cause of cancer-related deaths in women because most patients present with advanced stage disease at the time of diagnosis. Although cytoreductive surgery and platinum-based chemotherapy remain the gold standards of treatment, the recurrence rate of ovarian cancer remains high. Attempts to improve this standard two-drug chemotherapy by adding a third cytotoxic drug have failed to affect either progression-free survival or overall survival and have resulted in an increase in toxic side effects...
September 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28817445/the-safety-of-pembrolizumab-in-metastatic-melanoma-and-rheumatoid-arthritis
#11
Akshjot Puri, Jade Homsi
Immunotherapy has been in use for the treatment of melanoma since a very long time, but only recently have the cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody ipilimumab and programmed cell death-1 inhibitors such as nivolimumab and pembrolizumab been shown to induce marked improvements in survival in patients with metastatic melanoma. An important concern arises in terms of the safety of the use of these agents in patients with autoimmune diseases, solid organ transplant recipients on immunosuppression, patients with a history of previous hepatitis B or C, and patients with HIV infections as these patients were excluded from pivotal immunotherapy studies...
October 2017: Melanoma Research
https://www.readbyqxmd.com/read/28736183/immunotherapy-targeting-immune-check-point-s-in-brain-metastases
#12
Anna Maria Di Giacomo, Monica Valente, Alessia Covre, Riccardo Danielli, Michele Maio
Immunotherapy with monoclonal antibodies (mAb) directed to different immune check-point(s) is showing a significant clinical impact in a growing number of human tumors of different histotype, both in terms of disease response and long-term survival patients. In this rapidly changing scenario, treatment of brain metastases remains an high unmeet medical need, and the efficacy of immunotherapy in these highly dismal clinical setting remains to be largely demonstrated. Nevertheless, up-coming observations are beginning to suggest a clinical potential of cancer immunotherapy also in brain metastases, regardless the underlying tumor histotype...
July 13, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28727142/genomic-and-transcriptomic-heterogeneity-of-colorectal-tumours-arising-in-lynch-syndrome
#13
Hans Binder, Lydia Hopp, Michal R Schweiger, Steve Hoffmann, Frank Jühling, Martin Kerick, Bernd Timmermann, Susann Siebert, Christina Grimm, Lilit Nersisyan, Arsen Arakelyan, Maria Herberg, Peter Buske, Henry Loeffler-Wirth, Maciej Rosolowski, Christoph Engel, Jens Przybilla, Martin Peifer, Nicolaus Friedrichs, Gabriela Moeslein, Margarete Odenthal, Michelle Hussong, Sophia Peters, Stefanie Holzapfel, Jacob Nattermann, Robert Hueneburg, Wolff Schmiegel, Brigitte Royer-Pokora, Stefan Aretz, Michael Kloth, Matthias Kloor, Reinhard Buettner, Jörg Galle, Markus Loeffler
Colorectal cancer (CRC) arising in Lynch syndrome (LS) comprises tumours with constitutional mutations in DNA mismatch repair genes. There is still a lack of whole-genome and transcriptome studies of LS-CRC to address questions about similarities and differences in mutation and gene expression characteristics between LS-CRC and sporadic CRC, about the molecular heterogeneity of LS-CRC, and about specific mechanisms of LS-CRC genesis linked to dysfunctional mismatch repair in LS colonic mucosa and the possible role of immune editing...
October 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28721808/molecular-tests-for-the-choice-of-cancer-therapy
#14
Anna P Sokolenko, Evgeny N Imyanitov
There are over a dozen of approved cancer drugs, whose administration is tailored to predictive laboratory tests. The examples include estrogen and progesterone receptor status determination for the use of endocrine therapy, HER2 assessment for the administration of HER2-targeting agents, EGFR and ALK gene testing for lung cancer treatment, BRAF analysis in melanoma, etc. While first predictive tests relied on relatively easy laboratory procedures, more recent developments require rather sophisticated assays...
July 19, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28709816/-current-knowledge-on-perioperative-treatments-of-non-small-cell-lung-carcinomas
#15
REVIEW
S Brosseau, C Naltet, M Nguenang, V Gounant, P Mordant, B Milleron, Y Castier, G Zalcman
Surgery is still the main treatment in early-stage of non-small cell lung cancer with 5-year survival of stage IA patients exceeding 80%, but 5-year survival of stage II patients rapidly decreasing with tumor size, N status, and visceral pleura invasion. The major metastatic risk in such patients has supported clinical research assessing systemic or loco-regional perioperative treatments. Modern phase 3 trials clearly validated adjuvant or neo-adjuvant platinum-based chemotherapy in resected stage I-III patients as a standard treatment of which value has been reassessed several independent meta-analyses, showing a 5% benefit in 5y-survival, and a decrease of the relative risk for death around from 12 to 25%...
June 2017: Revue des Maladies Respiratoires
https://www.readbyqxmd.com/read/28686285/toward-a-structural-understanding-of-nucleic-acid-sensing-toll-like-receptors-in-the-innate-immune-system
#16
REVIEW
Zhikuan Zhang, Umeharu Ohto, Toshiyuki Shimizu
The history of mankind has been plagued by the tug of war with viral infections. Toll-like receptors (TLRs) and other receptors of the innate immune system constitute an early defense system against invading viruses by recognizing the viral genetic material, the nucleic acids (NAs). Agonistic ligands of NA-sensing TLRs play an emerging role in the treatment of viral diseases, demonstrating a crucial role of these receptors. Recently, crystal structures have afforded new insights into TLR recognition of NAs...
July 7, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28683527/host-directed-therapeutics-as-a-novel-approach-for-tuberculosis-treatment
#17
REVIEW
Ye-Ram Kim, Chul-Su Yang
Despite significant efforts to improve the treatment of tuberculosis (TB), it remains a prevalent infectious disease worldwide owing to the limitations of current TB therapeutic regimens. Recent work on novel TB treatment strategies has suggested that directly targeting host factors may be beneficial for TB treatment. Such strategies, termed host-directed therapeutics (HDTs), focus on host-pathogen interactions. HDTs may be more effective than the currently approved TB drugs, which are limited by the long durations of treatment needed and the emergence of drug-resistant strains...
September 28, 2017: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28645484/immune-check-point-inhibition-in-sarcomatoid-renal-cell-carcinoma-a-new-treatment-paradigm
#18
Ruben Raychaudhuri, Matthew J Riese, Kathryn Bylow, John Burfeind, Alexander C Mackinnon, Parag P Tolat, Kenneth A Iczkowski, Deepak Kilari
No abstract text is available yet for this article.
May 25, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28627792/%C3%AE-catenin-in-desmoid-type-fibromatosis-deep-insights-into-the-role-of-t41a-and-s45f-mutations-on-protein-structure-and-gene-expression
#19
Chiara Colombo, Antonino Belfiore, Nicholas Paielli, Loris De Cecco, Silvana Canevari, Erik Laurini, Maurizio Fermeglia, Sabrina Pricl, Paolo Verderio, Stefano Bottelli, Marco Fiore, Silvia Stacchiotti, Elena Palassini, Alessandro Gronchi, Silvana Pilotti, Federica Perrone
Desmoid-type fibromatosis (DF) is a rare mesenchymal lesion with high risk of local recurrence. Specific β-catenin mutations (S45F) appeared to be related to this higher risk compared to T41A-mutated or wild-type (WT). We explored the influence of both mutations and WT on structure stability and affinity of β-catenin for α-catenin and the pattern of gene expression that may influence DF behavior. Using 33 surgically resected primary DFs harboring T41A (n = 14), S45F (n = 10), or WT (n = 9), we performed a comparative molecular analysis by protein/protein interaction modeling, gene expression by DASL microarrays, human inflammation gene panel, and assessment of immune system-based biomarkers by immunohistochemistry...
June 19, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28603207/varied-immuno-related-adverse-events-induced-by-immune-check-point-inhibitors-nivolumab-associated-psoriasiform-dermatitis-related-with-increased-serum-level-of-interleukin-6
#20
REVIEW
Naoko Okiyama, Ryota Tanaka
  Nivolumab is a standard recombinant antibody treatment for patients with malignant melanoma (MM), which functions as an immune checkpoint inhibitor by blocking the programmed cell death-1 (PD-1) pathway in T cells. However, it leads to various immune-related adverse events (irAEs), and also exacerbates underlying autoimmune diseases. Herein we report cases of MM with irAE. Case 1: A 69-year-old woman with MM developed destructive thyroiditis resulting in hypothyroidism after 3 doses of nivolumab, and had been treated with thyroid gland auxiliary therapy...
2017: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
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