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- W4313365877 abstract "Abstract Background Invariant natural killer T (iNKT) cells are innate-like CD1d-restricted T cells that nucleate many anti-tumor immune pathways. In neuroblastoma (NB), a pediatric tumor of the sympathetic nervous system, intratumoral iNKT cell presence predicts better 5-year survival and prognosis. For optimal iNKT cell immunotherapy, an understanding of how they sustain effector function long-term within the tumor microenvironment (TME) is needed. Results Immunophenotyping of tumors from a mouse model of high-risk NB revealed a significant frequency of iNKT cells relative to conventional T cells (TCONV). To specifically redirect iNKT cell activity toward NB tumors, we developed a conjugate molecule (“CAb”) fusing a glycolipid antigen-loaded CD1d to an antibody directed against an NB-specific antigen. Acute CAb stimulation increased expression of cytokines and activation and degranulation markers specifically on intratumoral iNKT cells. Moreover, these expression levels were maintained upon chronic CAb stimulation. We postulate that iNKT cells can metabolically adapt to the nutrient-poor TME to withstand exhaustion. Transcriptional profiling of in vitro-stimulated iNKT cells and TCONV revealed differential expression patterns of genes in several metabolic pathways. We are now further defining the metabolic profile of iNKT cells and its link to anti-tumor function, and determining whether CAb activation of iNKT cells controls NB growth to improve survival. Conclusions iNKT cells within NB tumors can be activated and may possess unique metabolic and functional features from TCONV that confer sustained anti-tumor activity. Defining these properties will better inform the use of iNKT cells for solid tumor immunotherapy." @default.
- W4313365877 created "2023-01-06" @default.
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- W4313365877 date "2019-05-01" @default.
- W4313365877 modified "2023-09-26" @default.
- W4313365877 title "Harnessing the anti-tumor activity of invariant natural killer T cells for neuroblastoma immunotherapy" @default.
- W4313365877 doi "https://doi.org/10.4049/jimmunol.202.supp.134.17" @default.
- W4313365877 hasPublicationYear "2019" @default.
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