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

Autor:	Peng S; Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Blvd., Pasadena, CA 91125, USA., Zaretsky JM; Department of Medicine, University of California Los Angeles and Jonsson Comprehensive Cancer Center, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA., Ng AHC; Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Blvd., Pasadena, CA 91125, USA; Institute for Systems Biology, Seattle, WA 98109, USA., Chour W; Institute for Systems Biology, Seattle, WA 98109, USA; Division of Biology and Biological Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA., Bethune MT; Division of Biology and Biological Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA., Choi J; Institute for Systems Biology, Seattle, WA 98109, USA., Hsu A; Division of Biology and Biological Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA., Holman E; Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Blvd., Pasadena, CA 91125, USA., Ding X; Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Blvd., Pasadena, CA 91125, USA; Division of Biology and Biological Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA., Guo K; Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Blvd., Pasadena, CA 91125, USA., Kim J; Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Blvd., Pasadena, CA 91125, USA., Xu AM; Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Blvd., Pasadena, CA 91125, USA; Institute for Systems Biology, Seattle, WA 98109, USA., Heath JE; Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Blvd., Pasadena, CA 91125, USA., Noh WJ; Division of Biology and Biological Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA., Zhou J; Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Blvd., Pasadena, CA 91125, USA., Su Y; Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Blvd., Pasadena, CA 91125, USA; Institute for Systems Biology, Seattle, WA 98109, USA., Lu Y; Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Blvd., Pasadena, CA 91125, USA; Institute for Systems Biology, Seattle, WA 98109, USA., McLaughlin J; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA 90095, USA., Cheng D; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA 90095, USA., Witte ON; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA 90095, USA; Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, CA 90095, USA; Howard Hughes Medical Institute, University of California Los Angeles, Los Angeles, CA 90095, USA., Baltimore D; Division of Biology and Biological Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA., Ribas A; Department of Medicine, University of California Los Angeles and Jonsson Comprehensive Cancer Center, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA., Heath JR; Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Blvd., Pasadena, CA 91125, USA; Institute for Systems Biology, Seattle, WA 98109, USA. Electronic address: jheath@systemsbiology.org.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2019 Sep 03; Vol. 28 (10), pp. 2728-2738.e7.
DOI:	10.1016/j.celrep.2019.07.106
Abstrakt:	Neoantigen-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-specific T cell therapies and cancer vaccines. (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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