Cancer exosomes and natural killer cells dysfunction: biological roles, clinical significance and implications for immunotherapy

Mol Cancer. 2022 Jan 14;21(1):15. doi: 10.1186/s12943-021-01492-7.

Abstract

Tumor-derived exosomes (TDEs) play pivotal roles in several aspects of cancer biology. It is now evident that TDEs also favor tumor growth by negatively affecting anti-tumor immunity. As important sentinels of immune surveillance system, natural killer (NK) cells can recognize malignant cells very early and counteract the tumor development and metastasis without a need for additional activation. Based on this rationale, adoptive transfer of ex vivo expanded NK cells/NK cell lines, such as NK-92 cells, has attracted great attention and is widely studied as a promising immunotherapy for cancer treatment. However, by exploiting various strategies, including secretion of exosomes, cancer cells are able to subvert NK cell responses. This paper reviews the roles of TDEs in cancer-induced NK cells impairments with mechanistic insights. The clinical significance and potential approaches to nullify the effects of TDEs on NK cells in cancer immunotherapy are also discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biological Transport
  • Biomarkers
  • Cell Communication
  • Cell Survival
  • Cytokines / metabolism
  • Cytotoxicity, Immunologic
  • Disease Management
  • Disease Susceptibility / immunology
  • Energy Metabolism
  • Exosomes / metabolism*
  • Gene Expression Regulation
  • Humans
  • Immunotherapy
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism*
  • NK Cell Lectin-Like Receptor Subfamily K / metabolism
  • Neoplasms / etiology*
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Protein Binding
  • Signal Transduction

Substances

  • Biomarkers
  • Cytokines
  • NK Cell Lectin-Like Receptor Subfamily K