In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. 3569-3569
Abstract:
Adoptive Cell Therapies (ACT) with T cell receptor-engineered (TCReng) T cells have shown promising results. Unfortunately, for a fuller understanding of their biology, currently available immunological assays have proven inadequate. Given that RNA-Seq using Next Generation Sequencing (NGS) offers substantial opportunities, we carried out NGS of the MART-127-35 specific TCReng human primary CD8+ and CD4+ T-cells following cognate stimulation, to obtain a comprehensive understanding of the transcriptional signatures underlying their biology. Data analyses revealed approximately 30,000 transcripts, a sizeable number of which showing up- or down-regulation covering virtually all relevant aspects of T cell biology (i.e., effector function, differentiation, proliferative activities, apoptosis, etc.) when stimulated by the cognate epitope. The transcriptional profiles of the TCReng CD8+ and CD4+ T cells were found to be remarkably similar. Additionally, 72,000 known isoforms and about 20,000 previously undescribed isoforms were detected. Interestingly, a number of long noncoding RNAs (lncRNA) - some with known functions (e.g., NEAT1 and MALAT1, both implicated in RNA editing, were up-regulated in the two cell types), and others with unknown function (e.g., GAS5, MIAT, and FTX showing modulations in expression), were also detected in both cell types. Although a comprehensive knowledge of the transcriptional signatures and a clear understanding of the spliced variants, the novel isoforms, and the lncRNAs in T cell biology will require further work, our study shows that NGS of specific epitope reactive T cells will be a very useful tool in deciphering the transcriptional controls underlying the function and the fate of epitope specific anti-tumor T cells. Citation Format: Prashant Singh, Nitya G. Chakraborty, Umar Farooq, Upendra P. Hegde, Richard Everson, David I. Dorsky, Bijay Mukherji. Transcriptional signatures in human melanoma epitope MART-127-35 specific TCR-engineered T cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3569. doi:10.1158/1538-7445.AM2014-3569
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2014-3569
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2014
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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