Generation and Harnessing of Heterotypic Tumor-Stroma Spheroids to Study Cancer Immunosurveillance

Methods Mol Biol. 2019;1884:269-281. doi: 10.1007/978-1-4939-8885-3_19.

Abstract

Clinically apparent tumors have often established an immunosuppressive tumor microenvironment which renders them "cold," meaning that there are low numbers of immune cells within the tumor. Consequently, novel immunotherapy approaches such as checkpoint inhibitors fail to reactivate the tumor-targeted immune cells. Here we describe the generation of heterotypic tumor-stroma spheroids to study various approaches aiming at the reactivation of cancer immunosurveillance. These spheroids allow to investigate whether a certain immunotherapy or a combination treatment is able to stimulate antitumor immunity in poorly immunological ("cold") tumors, by increasing the number of tumor-infiltrating immune cells ("hot" tumors).

Keywords: ADCC; CAR-T; CXCL12; Cancer immunosurveillance; Checkpoint inhibitor; Immune cell infiltration; PD-1; T cell exclusion; Tumor infiltrating lymphocytes; Tumor-stroma spheroid.

MeSH terms

  • Animals
  • Aptamers, Nucleotide / pharmacology
  • Blood Buffy Coat / cytology
  • Cell Culture Techniques / instrumentation
  • Cell Culture Techniques / methods*
  • Chemokine CXCL12 / antagonists & inhibitors
  • Chemokine CXCL12 / genetics
  • Chemokine CXCL12 / immunology
  • Flow Cytometry / instrumentation
  • Flow Cytometry / methods
  • HT29 Cells
  • Healthy Volunteers
  • Humans
  • Immunologic Surveillance*
  • Immunotherapy, Adoptive / methods
  • Leukocytes, Mononuclear / immunology
  • Mice
  • Neoplasms / drug therapy
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Receptors, Chimeric Antigen / immunology
  • Spheroids, Cellular / drug effects
  • Spheroids, Cellular / immunology
  • Stromal Cells / drug effects
  • Stromal Cells / immunology
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / immunology*

Substances

  • Aptamers, Nucleotide
  • CXCL12 protein, human
  • Chemokine CXCL12
  • NOX-A12
  • Receptors, Chimeric Antigen