6,761 research outputs found
Precision targeting of human iNKT cells for cancer immunotherapy
No full textInvariant natural killer T (iNKT) cells are a distinct subset of T lymphocytes that recognise lipid antigens presented by CD1d. iNKT cells have been classified into subsets based on both their TCR affinity for CD1d and coreceptor expression, such as CD4⁺ and double-negative (DN) populations, each with distinct functional properties. However, their differential roles in anti-tumour immunity remain unclear. To address this, we employed single-cell RNA sequencing to compare the gene expression and transcription factor profiles of low and high affinity iNKT cells, revealing distinct molecular signatures. TCR sequencing using Oxford Nanopore technology uncovered substantial variability,particularly within the complementarity-determining region 3 (CDR3) of both the α and βchains. Functional assays demonstrated that high affinity iNKT clones exhibit superior cytotoxicity against CD1d-expressing target cells. Additionally, we found that DN iNKT cells display greater cytotoxic potential than CD4⁺ iNKT cells, correlating with their strong expression of the activating receptor NKG2D. Blocking experiments confirmed that NKG2D mediates their enhanced tumour cell lysis. Given the importance of CD1d in iNKT cell activation, we explored strategies to enhance its expression on cancer cells. We optimised an in vitro treatment regimen combining Enhancer of Zeste Homolog 2 (EZH2) inhibitors and all-trans-retinoic acid (ATRA),demonstrating that this approach significantly increases CD1d surface expression and enhances iNKT cell-mediated lysis of acute myeloid leukaemia (AML) cells. Collectively, our findings underscore the functional and phenotypic heterogeneity of iNKT cells and their significance in cancer immunotherapy. Selectively targeting specific iNKT subsets may enhance therapeutic efficacy, while tumour micro environment modulation to upregulate CD1d could further improve direct iNKT-mediated tumour lysis. Future studies should optimise these strategies for clinical application in cancer immunotherapy
Adrian Caesar speaking at Alex Miller author: A Celebration, held at the National Library, Canberra, 30 October 2011 /
No full textTitle from information supplied by photographer.; Part of the collection: Alex Miller author: A Celebration, held at the National Library of Australia theatre, 30 October 2011.; Mode of access: Online.; Photographed by a staff member of the National Library of Australia
[Letter from Alex Bradford to Lieutenant and Mrs. Ray Starner - November 4, 1940]
No full textLetter from Alex Bradford to Lieutenant and Mrs. Ray Starner describing the the current state of affairs that the author was experiencing, including: the London blitz, the moral of the troops on the ground, and the collective company of men opposing the Nazi regime
Dataset supporting thesis titled "Precision targeting of human iNKT cells for cancer immunotherapy"
No full textRaw data, processed data and images generated during this thesis project. </span
Alex Haley, author
No full textExamines the life and achievements of Alex Haley, celebrated author of "Roots" and other writings, discussing his life and literary career, as well as his obsession with researching his family's history
Article on the lack of affordable housing in Portland, describing author Alex Ir
No full textArticle on the lack of affordable housing in Portland, describing author Alex Irvine\u27s two-week search for an affordable two-bedroom apartment. According to the Department of Housing and Urban Development\u27s recommendation that no more than 30 percent of your income be spent on housing, Irvine and his family of four should look for an apartment renting for 900, down from 36,000. Portland\u27s 2002 comprehensive housing plan\u27s goal of 4,200 new units by 2012, seems unrealistic even to Mark Adelson, former city housing director. Details
Description by author Alex Irvine of his recent participation in the San Diego C
No full textDescription by author Alex Irvine of his recent participation in the San Diego Comic-Con, one of the largest conferences of comic/media/book producers and consumers. Irvine was there to promote his new fiction book, One King, One Soldier, published by Del Rey
Recovery through contradiction?
No full textWith this new drug strategy, the circle has turned. It was a Conservative government
that introduced the first drug strategy, Tackling Drugs Together, in 1995. This aimed
to reduce drug related crime, protect young people and reduce health harms by
discouraging drug use. It was criticised at the time for having unrealistic, intangible
aims and for not providing the necessary funding. New Labour’s strategies introduced
increasingly specific targets and massively expanded the funding of treatment. This
new Coalition strategy has no targets and provides no new funding
Alex Miller signing books at the National Library of Australia, Canberra, 30 October 2011 /
No full textTitle from information supplied by photographer.; Part of the collection: Alex Miller author: A Celebration, held at the National Library of Australia theatre, 30 October 2011.; Mode of access: Online.; Photographed by a staff member of the National Library of Australia
Alex Miller taking questions at the National Library of Australia, Canberra, 30 October 2011 /
No full textTitle from information supplied by photographer.; Part of the collection: Alex Miller author: A Celebration, held at the National Library of Australia theatre, 30 October 2011.; Mode of access: Online.; Photographed by a staff member of the National Library of Australia
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