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Li, Bo

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Li, Bo
Author's Publications: search.filters.isAuthorOfPublication.7bb4c783-b88b-4996-a8cb-1aee9509d685

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    Publication
    Landscape of tumor-infiltrating T cell repertoire of human cancers
    (2016) Li, Bo; Li, Taiwen; Pignon, Jean-Christophe; Wang, Binbin; Wang, Jinzeng; Shukla, Sachet; Dou, Ruoxu; Chen, Qianming; Hodi, F. Stephen; Choueiri, Toni K.; Wu, Catherine; Hacohen, Nir; Signoretti, Sabina; Liu, Jun; Liu, X. Shirley
    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 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.
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    Publication
    Comprehensive analyses of tumor immunity: implications for cancer immunotherapy
    (BioMed Central, 2016) Li, Bo; Severson, Eric; Pignon, Jean-Christophe; Zhao, Haoquan; Li, Taiwen; Novak, Jesse; Jiang, Peng; Shen, Hui; Aster, Jon; Rodig, Scott; Signoretti, Sabina; Liu, Jun; Liu, X. Shirley
    Background: Understanding the interactions between tumor and the host immune system is critical to finding prognostic biomarkers, reducing drug resistance, and developing new therapies. Novel computational methods are needed to estimate tumor-infiltrating immune cells and understand tumor–immune interactions in cancers. Results: We analyze tumor-infiltrating immune cells in over 10,000 RNA-seq samples across 23 cancer types from The Cancer Genome Atlas (TCGA). Our computationally inferred immune infiltrates associate much more strongly with patient clinical features, viral infection status, and cancer genetic alterations than other computational approaches. Analysis of cancer/testis antigen expression and CD8 T-cell abundance suggests that MAGEA3 is a potential immune target in melanoma, but not in non-small cell lung cancer, and implicates SPAG5 as an alternative cancer vaccine target in multiple cancers. We find that melanomas expressing high levels of CTLA4 separate into two distinct groups with respect to CD8 T-cell infiltration, which might influence clinical responses to anti-CTLA4 agents. We observe similar dichotomy of TIM3 expression with respect to CD8 T cells in kidney cancer and validate it experimentally. The abundance of immune infiltration, together with our downstream analyses and findings, are accessible through TIMER, a public resource at http://cistrome.org/TIMER. Conclusions: We develop a computational approach to study tumor-infiltrating immune cells and their interactions with cancer cells. Our resource of immune-infiltrate levels, clinical associations, as well as predicted therapeutic markers may inform effective cancer vaccine and checkpoint blockade therapies. Electronic supplementary material The online version of this article (doi:10.1186/s13059-016-1028-7) contains supplementary material, which is available to authorized users.
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    Publication
    A Peripheral Immune Signature of Responsiveness to PD-1 Blockade in Patients With Classical Hodgkin Lymphoma
    (Springer Science and Business Media LLC, 2020-08-10) Cader, Fathima Zumla; Hu, Xihao; Goh, Walter L.; Wienand, Kirsty; Ouyang, Jing; Mandato, Elisa; Redd, Robert; Lawton, Lee; Chen, Pei-Hsuan; Weirather, Jason L.; Schackmann, Ron C. J.; Li, Bo; Ma, Wenjiang; Armand, Philippe; Rodig, Scott; Neuberg, Donna; Liu, X. Shirley; Shipp, Margaret A.; shipp
    PD-1 blockade is highly effective in classical Hodgkin lymphoma although the mechanism of action in this largely MHC class I-negative tumor remains undefined. Given this conundrum, we utilized the complementary approaches of T-cell receptor (TCR) sequencing and cytometry by time-of-flight analysis to obtain a peripheral immune signature of responsiveness to PD-1 blockade in clinical trial patients. Increased total and CD4+ TCR repertoire diversity and clonal expansion of singleton T cells were associated with response to anti PD-1 therapy. Additionally, responding patients had an increased abundance of activated NK cells and a newly identified CD3-CD68+CD4+GrB+ subset suggesting a complementary role for innate immunity in the efficacy of PD-1 blockade.