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Immunoncology

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https://www.readbyqxmd.com/read/29100397/correlating-programmed-death-ligand-1-pd-l1-expression-mismatch-repair-deficiency-and-outcomes-across-tumor-types-implications-for-immunotherapy
#1
Seung Tae Kim, Samuel J Klempner, Se Hoon Park, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Won Ki Kang, Kyoung-Mee Kim, Jeeyun Lee
The identification of biomarkers associated with response to therapeutic agents is central to optimizing patient outcomes. Expression of the immune checkpoint proteins PD-1/L1, and DNA mismatch repair deficiency (dMMR) status may be predictive response biomarkers for immunotherapies, but their overlap requires further study. We prospectively conducted PD-L1 and MMR immunohistochemistry (IHC) on 430 consecutive patients with advanced gastrointestinal (GI) cancers, genitourinary (GU) cancers or rare cancers between June 2012 and March 2016...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28940468/the-catalytic-mechanism-of-cyclic-gmp-amp-synthase-cgas-and-implications-for-innate-immunity-and-inhibition
#2
Justin Hall, Erik C Ralph, Suman Shanker, Hong Wang, Laura J Byrnes, Reto Horst, Jimson Wong, Amy Brault, Darren Dumlao, James F Smith, Leslie A Dakin, Daniel C Schmitt, John Trujillo, Fabien Vincent, Matt Griffor, Ann E Aulabaugh
Cyclic GMP-AMP synthase (cGAS) is activated by ds-DNA binding to produce the secondary messenger 2',3'-cGAMP. cGAS is an important control point in the innate immune response; dysregulation of the cGAS pathway is linked to autoimmune diseases while targeted stimulation may be of benefit in immunoncology. We report here the structure of cGAS with dinucleotides and small molecule inhibitors, and kinetic studies of the cGAS mechanism. Our structural work supports the understanding of how ds-DNA activates cGAS, suggesting a site for small molecule binders that may cause cGAS activation at physiological ATP concentrations, and an apparent hotspot for inhibitor binding...
December 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/26661378/il-10-expanding-the-immune-oncology-horizon
#3
Ivan H Chan, Victoria Wu, Scott McCauley, Elizabeth A Grimm, John B Mumm
Recent advances in immunoncology have dramatically changed the treatment options available to cancer patients. However, the fundamental challenges with this therapeutic modality are not new and still persist with the current wave of immunoncology compounds. These challenges are centered on the activation and expansion, induction of intratumoral infiltration and persistence of highly activated, cytotoxic, tumor antigen specific CD8+ T cells. We have investigated the anti-tumor mechanism of action of pegylated recombinant interleukin-10, (PEG-rIL-10) both pre-clinically with murine (PEG-rMuIL-10) and now clinically (AM0010) with human pegylated interleukin-10...
2015: Receptors & Clinical Investigation
https://www.readbyqxmd.com/read/24884790/inference-of-high-resolution-hla-types-using-genome-wide-rna-or-dna-sequencing-reads
#4
Yu Bai, Min Ni, Blerta Cooper, Yi Wei, Wen Fury
BACKGROUND: Accurate HLA typing at amino acid level (four-digit resolution) is critical in hematopoietic and organ transplantations, pathogenesis studies of autoimmune and infectious diseases, as well as the development of immunoncology therapies. With the rapid adoption of genome-wide sequencing in biomedical research, HLA typing based on transcriptome and whole exome/genome sequencing data becomes increasingly attractive due to its high throughput and convenience. However, unlike targeted amplicon sequencing, genome-wide sequencing often employs a reduced read length and coverage that impose great challenges in resolving the highly homologous HLA alleles...
2014: BMC Genomics
https://www.readbyqxmd.com/read/24173315/evaluation-of-cancer-immunity-in-mice
#5
Mary L Disis, Karolina Palucka
There have been significant advances in the development and application of novel therapeutic approaches and improved diagnostics for cancer in the past decade. Manipulation and/or assessment of cancer-specific immunity have been central to these advances. Murine models are a standard for the preclinical development of cancer immunotherapeutics. However, critical advances in our understanding of the role of the immune microenvironment and the assessment of cancer-specific immunity have not been fully applied to rodent models...
March 1, 2014: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/1229818/-attempts-at-the-introduction-of-a-clinico-immunological-therapy-for-malignant-tumors
#6
A Ferstl
The basis for an immunoncological therapy was investigated by culture of lymphocytes incubated with autologous tumor-antigen. The methods of isolation and cultivation are adapted to conditions of reinfusion. The effectiveness of tumor-aggressive action is demonstrated as transformation to lymphoblasts (indirect action) and tumor-cytolysis (direct action) in mixed lymphocyte-tumorcell culture.
1975: Acta Medica Austriaca
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