Landscape of innate lymphoid cells in human head and neck cancer reveals divergent NK cell states in the tumor microenvironment

  • Uriel Y. Moreno-Nieves
    Department of Otolaryngology—Head and Neck Surgery, Stanford Cancer Institute, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305;
  • Joshua K. Tay
    Department of Otolaryngology—Head and Neck Surgery, Stanford Cancer Institute, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305;
  • Saumyaa Saumyaa
    Department of Otolaryngology—Head and Neck Surgery, Stanford Cancer Institute, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305;
  • Nina B. Horowitz
    Department of Otolaryngology—Head and Neck Surgery, Stanford Cancer Institute, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305;
  • June Ho Shin
    Department of Otolaryngology—Head and Neck Surgery, Stanford Cancer Institute, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305;
  • Imran A. Mohammad
    Department of Otolaryngology—Head and Neck Surgery, Stanford Cancer Institute, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305;
  • Bogdan Luca
    Department of Biomedical Data Science, Stanford Cancer Institute, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305;
  • David C. Mundy
    Department of Otolaryngology—Head and Neck Surgery, Stanford Cancer Institute, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305;
  • Gunsagar S. Gulati
    Department of Biomedical Data Science, Stanford Cancer Institute, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305;
  • Nikita Bedi
    Department of Otolaryngology—Head and Neck Surgery, Stanford Cancer Institute, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305;
  • Serena Chang
    Department of Otolaryngology—Head and Neck Surgery, Stanford Cancer Institute, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305;
  • Chen Chen
    Department of Otolaryngology—Head and Neck Surgery, Stanford Cancer Institute, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305;
  • Michael J. Kaplan
    Department of Otolaryngology—Head and Neck Surgery, Stanford Cancer Institute, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305;
  • Eben L. Rosenthal
    Department of Otolaryngology—Head and Neck Surgery, Stanford Cancer Institute, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305;
  • F. Christopher Holsinger
    Department of Otolaryngology—Head and Neck Surgery, Stanford Cancer Institute, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305;
  • Vasu Divi
    Department of Otolaryngology—Head and Neck Surgery, Stanford Cancer Institute, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305;
  • Fred M. Baik
    Department of Otolaryngology—Head and Neck Surgery, Stanford Cancer Institute, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305;
  • Davud B. Sirjani
    Department of Otolaryngology—Head and Neck Surgery, Stanford Cancer Institute, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305;
  • Andrew J. Gentles
    Department of Biomedical Data Science, Stanford Cancer Institute, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305;
  • Aaron M. Newman
    Department of Biomedical Data Science, Stanford Cancer Institute, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305;
  • Aharon G. Freud
    Department of Pathology, The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210
  • John B. Sunwoo
    Department of Otolaryngology—Head and Neck Surgery, Stanford Cancer Institute, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305;

抄録

<jats:title>Significance</jats:title> <jats:p>NK cells have been observed to be present within most solid tumors, but the antitumor activity of the intratumoral NK cells has been unclear. In this study, we examined the entire spectrum of innate lymphoid cells within primary human tumors and demonstrate that peripheral NK cells in the tumor microenvironment differentiate into heterogeneous cell states, resulting in either a hyporesponsive NK cell subset or a highly active NK cell phenotype that closely resembles intraepithelial ILC1s and that has potent antitumor properties. Importantly, this differentiation into ieILC1-like cells occurs when NK cells are cocultured with epithelial cells, providing important information for NK cell immunotherapy approaches.</jats:p>

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