Assessing the Impact of Phytochemicals on Immune Checkpoints: Implications for Cancer Immunotherapy

Methods Mol Biol. 2020:2111:161-173. doi: 10.1007/978-1-0716-0266-9_14.

Abstract

Phytochemicals are the basis for many anticancer drugs currently in clinical use, as well as a potential source of future cancer treatments. Some phytochemicals have been found to modify the expression of checkpoint inhibitors of the immune response, as well as kill cancer cells. Cancer cells, in turn, may evade detection by the immune system by expressing molecules such as programmed death ligand 1 (PD-L1) that interacts with programmed cell death 1 (PD-1) on T cells to inhibit T cell activation and effector function. Phytochemicals have direct effects on cancer cells and/or T cells that may impact PD-L1/PD1 interactions, although this may vary depending on the phytochemical in question. Flow cytometric analysis of cancer cells stained with anti-PD-L1 antibodies following treatment with a given phytochemical enables the detection of any alteration in PD-L1 expression. The effect of the phytochemical on T cell function can be assessed using proliferation assays (e.g., tritiated thymidine incorporation, flow cytometric analysis of Oregon Green 488-stained cells) and enzyme-linked immunosorbent assay of interleukin-2 content in culture supernatants. Additional study is needed to better understand the impact of phytochemicals on cancer immunotherapy.

Keywords: Cancer; Co-cultures; Flow cytometry; Immune checkpoints; Immunotherapy; Interleukin-2; Proliferation; T cells.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • B7-H1 Antigen / metabolism*
  • Cell Adhesion
  • Cell Proliferation / drug effects
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Immunotherapy
  • Jurkat Cells
  • Lymphocyte Activation / drug effects
  • Mice
  • Neoplasms / drug therapy
  • Neoplasms / immunology*
  • Phytochemicals / pharmacology*
  • Phytochemicals / therapeutic use
  • Programmed Cell Death 1 Receptor / metabolism*
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / metabolism

Substances

  • Antineoplastic Agents
  • B7-H1 Antigen
  • CD274 protein, human
  • PDCD1 protein, human
  • Phytochemicals
  • Programmed Cell Death 1 Receptor