Polymorphonuclear Myeloid-Derived Suppressor Cells Are Abundant in Peripheral Blood of Cancer Patients and Suppress Natural Killer Cell Anti-Tumor Activity

Front Immunol. 2022 Jan 18:12:803014. doi: 10.3389/fimmu.2021.803014. eCollection 2021.

Abstract

Tumor microenvironment (TME) includes a wide variety of cell types and soluble factors capable of suppressing immune-responses. While the role of NK cells in TME has been analyzed, limited information is available on the presence and the effect of polymorphonuclear (PMN) myeloid-derived suppressor cells, (MDSC). Among the immunomodulatory cells present in TME, MDSC are potentially efficient in counteracting the anti-tumor activity of several effector cells. We show that PMN-MDSC are present in high numbers in the PB of patients with primary or metastatic lung tumor. Their frequency correlated with the overall survival of patients. In addition, it inversely correlated with low frequencies of NK cells both in the PB and in tumor lesions. Moreover, such NK cells displayed an impaired anti-tumor activity, even those isolated from PB. The compromised function of NK cells was consequent to their interaction with PMN-MDSC. Indeed, we show that the expression of major activating NK receptors, the NK cytolytic activity and the cytokine production were inhibited upon co-culture with PMN-MDSC through both cell-to-cell contact and soluble factors. In this context, we show that exosomes derived from PMN-MDSC are responsible of a significant immunosuppressive effect on NK cell-mediated anti-tumor activity. Our data may provide a novel useful tool to implement the tumor immunoscore. Indeed, the detection of PMN-MDSC in the PB may be of prognostic value, providing clues on the presence and extension of both adult and pediatric tumors and information on the efficacy not only of immune response but also of immunotherapy and, possibly, on the clinical outcome.

Keywords: biomarker; immunoscore; lung tumor; myeloid-derived suppressor cell; natural killer.

Publication types

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

MeSH terms

  • Biomarkers
  • Cell Communication / immunology
  • Cell Communication / physiology
  • Cytotoxicity, Immunologic
  • Gene Expression Profiling
  • Humans
  • Immunomodulation
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism*
  • Leukocyte Count*
  • Lung Neoplasms / etiology
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Myeloid-Derived Suppressor Cells / immunology*
  • Myeloid-Derived Suppressor Cells / metabolism*
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Neoplasms / etiology
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neutrophils / immunology*
  • Neutrophils / metabolism*
  • Tumor Microenvironment / immunology

Substances

  • Biomarkers