Li, BoLi, TaiwenPignon, Jean-ChristopheWang, BinbinWang, JinzengShukla, SachetDou, RuoxuChen, QianmingHodi, F. StephenChoueiri, Toni K.Wu, CatherineHacohen, NirSignoretti, SabinaLiu, JunLiu, X. Shirley2017-03-282016Li, B., T. Li, J. Pignon, B. Wang, J. Wang, S. Shukla, R. Dou, et al. 2016. “Landscape of tumor-infiltrating T cell repertoire of human cancers.” Nature genetics 48 (7): 725-732. doi:10.1038/ng.3581. http://dx.doi.org/10.1038/ng.3581.http://nrs.harvard.edu/urn-3:HUL.InstRepos:31731849We 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 thousand CDR3 sequences, including 15% with full-length. CDR3 sequence length distribution and amino acid conservation, as well as variable gene usage of infiltrating T-cells in many tumors, except brain and kidney cancers, resembled those in the peripheral blood of healthy donors. We observed a strong association between T-cell diversity and tumor mutation load, and predicted SPAG5 and TSSK6 as putative immunogenic cancer/testis antigens in multiple cancers. Finally, we identified 3 potential immunogenic somatic mutations based on their co-occurrence with CDR3 sequences. One of them, PRAMEF4 F300V, was predicted to bind strongly to both MHC-I and MHC-II, with matched HLA types in its carriers. Our analyses have the potential to simultaneously identify immunogenic neoantigens and the tumor-reactive T-cell clonotypes.en-USJournal Article2017-03-2810.1038/ng.3581