Paper - Review

DOI: 10.1038/ng.3581

Abstract

Developed → a computational method
→ to infer the complementarity-determining region 3 (CDR3) sequences ← of tumor-infiltrating T-cells
← in > 9K RNA-seq samples ← across 29 cancer types

Identified → > 600K CDR3 sequences
← including 15% that were full length

1⃣ CDR3 sequence length distribution 2⃣ amino acid conservation
→ for infiltrating T-cells ← in many tumors
→ except in 1⃣ brain 2⃣ kidney cancers
→ resembled those → for peripheral blood cells ← from healthy donors

Observed → a strong association
← between 1⃣ T-cell diversity 2⃣ tumor mutation load

Predicted → 1⃣ SPAG5 2⃣ TSSK6
← as putative immunogenic cancer/testis antigens ← in multiple cancers

Identified → three potential immunogenic somatic mutations
← on the basis of their co-occurrence with CDR3 sequences

p.Phe300Val
← a PRAMEF4 mutation encoding
→ was predicted → to result in peptide binding strongly
→ to both 1⃣ MHC class I 2⃣ MHC class II molecules
← with matched HLA types in its carriers

❗: identify → 1⃣ immunogenic neoantigens 2⃣ tumor-reactive T-cell clonotypes

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