Elucidating the role of an immunomodulatory protein in cancer: From protein expression to functional characterization

Methods Enzymol. 2019:629:307-360. doi: 10.1016/bs.mie.2019.05.053. Epub 2019 Jun 20.

Abstract

Several fundamental discoveries made over the last two decades, in the field of cancer biology, have increased our understanding of the complex tumor micro- and macroenvironments. This has shifted the current empirical cancer therapies to more rationalized treatments targeting immunomodulatory proteins. From the point of identification, a protein target undergoes several interrogations, which are necessary to truly define its druggability. Here, we outline some basic steps that can be followed for in vitro characterization of a potential immunomodulatory protein target. We describe procedures for recombinant protein expression and purification including key annotations on protein cloning, expression systems, purification strategies and protein characterization using structural and biochemical approaches. For functional characterization, we provide detailed protocols for using flow-cytometric techniques in cell lines or primary cells to study protein expression profiles, proliferation, apoptosis and cell-cycle changes. This multilevel approach can provide valuable, in-depth understanding of any protein target with potential immunomodulatory effects.

Keywords: Apoptosis assay; Cell-based protein expression analysis; Cell-cycle arrest; Cloning; Flow cytometry; Proliferation assay; Protein characterization; Protein tags; Recombinant protein overexpression; Recombinant protein purification.

MeSH terms

  • Animals
  • Apoptosis / immunology
  • Cell Cycle / immunology
  • Cell Line, Tumor
  • Cell Proliferation
  • Flow Cytometry / methods*
  • Gene Expression Regulation, Neoplastic / immunology
  • Humans
  • Mice
  • Neoplasms / genetics
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Primary Cell Culture / methods
  • Proteomics / methods*
  • Recombinant Proteins / immunology
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism

Substances

  • Recombinant Proteins