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Landscape of Tumor-Infiltrating T Cell Repertoire of Human Cancers
Oleh:
Bo Li
;
Taiwen Li
;
Pignon, Jean-Christophe
;
Binbin Wang
;
Jinzeng Wang
Jenis:
Article from Journal - ilmiah internasional
Dalam koleksi:
Nature Genetics vol. 48 no. 07 (Jul. 2016)
,
page 725-732.
Topik:
Cancer Microenvironment
;
Data Mining
;
Immunosurveillance
;
Immunotherapy
Ketersediaan
Perpustakaan FK
Nomor Panggil:
N12.K
Non-tandon:
1 (dapat dipinjam: 0)
Tandon:
tidak ada
Lihat Detail Induk
Isi artikel
We developed a computational method to infer the complementarity-determining region 3 (CDR3) sequences of tumor-infiltrating T cells in 9,142 RNA-seq samples across 29 cancer types. We identified over 600,000 CDR3 sequences, including 15% that were full length. CDR3 sequence length distribution and amino acid conservation, as well as variable gene usage, for infiltrating T cells in many tumors, except in brain and kidney cancers, resembled those for peripheral blood cells from healthy donors. We observed a strong association between T cell diversity and tumor mutation load, and we predicted SPAG5 and TSSK6 as putative immunogenic cancer/testis antigens in multiple cancers. Finally, we identified three potential immunogenic somatic mutations on the basis of their co-occurrence with CDR3 sequences. One of them, a PRAMEF4 mutation encoding p.Phe300Val, was predicted to result in peptide binding strongly to both MHC class I and class II molecules, with matched HLA types in its carriers. Our analyses have the potential to simultaneously identify immunogenic neoantigens and tumor-reactive T cell clonotypes.
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