The acidic microenvironment as a possible niche of dormant tumor cells

Cell Mol Life Sci. 2017 Aug;74(15):2761-2771. doi: 10.1007/s00018-017-2496-y. Epub 2017 Mar 22.

Abstract

Although surgical excision, chemo-, and radio-therapy are clearly advanced, tumors may relapse due to cells of the so-called "minimal residual disease". Indeed, small clusters of tumor cells persist in host tissues after treatment of the primary tumor elaborating strategies to survive and escape from immunological attacks before their relapse: this variable period of remission is known as "cancer dormancy". Therefore, it is crucial to understand and consider the major concepts addressing dormancy, to identify new targets and disclose potential clinical strategies. Here, we have particularly focused the relationships between tumor microenvironment and cancer dormancy, looking at a re-appreciated aspect of this compartment that is the low extracellular pH. Accumulating evidences indicate that acidity of tumor microenvironment is associated with a poor prognosis of tumor-bearing patients, stimulates a chemo- and radio-therapy resistant phenotype, and suppresses the tumoricidal activity of cytotoxic lymphocytes and natural killer cells, and all these aspects are useful for dormancy. Therefore, this review discusses the possibility that acidity of tumor microenvironment may provide a new, not previously suggested, adequate milieu for "dormancy" of tumor cells.

Keywords: Acidosis; Dormancy; Tumor microenvironment.

Publication types

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

MeSH terms

  • Acidosis / complications*
  • Acidosis / immunology
  • Acidosis / pathology
  • Animals
  • Apoptosis
  • Cell Proliferation
  • Humans
  • Hydrogen-Ion Concentration
  • Immunologic Surveillance
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / pathology
  • Neoplasm Recurrence, Local / etiology*
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm, Residual / complications
  • Neoplasm, Residual / immunology
  • Neoplasm, Residual / pathology
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Neoplastic Stem Cells / immunology
  • Neoplastic Stem Cells / pathology
  • Neovascularization, Pathologic / etiology
  • Neovascularization, Pathologic / immunology
  • Neovascularization, Pathologic / pathology
  • Prognosis
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / pathology
  • Tumor Microenvironment*