Sensitive Detection and Analysis of Neoantigen-Specific T Cell Populations from Tumors and Blood

Publication date: 3 September 2019Source: Cell Reports, Volume 28, Issue 10Author(s): Songming Peng, Jesse M. Zaretsky, Alphonsus H.C. Ng, William Chour, Michael T. Bethune, Jongchan Choi, Alice Hsu, Elizabeth Holman, Xiaozhe Ding, Katherine Guo, Jungwoo Kim, Alexander M. Xu, John E. Heath, Won Jun Noh, Jing Zhou, Yapeng Su, Yue Lu, Jami McLaughlin, Donghui Cheng, Owen N. WitteSummaryNeoantigen-specific T cells are increasingly viewed as important immunotherapy effectors, but physically isolating these rare cell populations is challenging. Here, we describe a sensitive method for the enumeration and isolation of neoantigen-specific CD8+ T cells from small samples of patient tumor or blood. The method relies on magnetic nanoparticles that present neoantigen-loaded major histocompatibility complex (MHC) tetramers at high avidity by barcoded DNA linkers. The magnetic particles provide a convenient handle to isolate the desired cell populations, and the barcoded DNA enables multiplexed analysis. The method exhibits superior recovery of antigen-specific T cell populations relative to literature approaches. We applied the method to profile neoantigen-specific T cell populations in the tumor and blood of patients with metastatic melanoma over the course of anti-PD1 checkpoint inhibitor therapy. We show that the method has value for monitoring clinical responses to cancer immunotherapy and might help guide the development of personalized mutational neoantigen-spec...
Source: Cell Reports - Category: Cytology Source Type: research

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