Advertisement

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

  • Melanie R. Power Coombs
  • David W. HoskinEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 2111)

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.

Key words

Cancer Co-cultures Flow cytometry Immune checkpoints Immunotherapy Interleukin-2 Proliferation T cells 

References

  1. 1.
    Forward NA, Conrad DM, Power Coombs MR, Doucette CD, Furlong SJ, Lin T-J, Hoskin DW (2011) Curcumin blocks interleukin (IL)-2 signaling in T-lymphocytes by inhibiting IL-2 synthesis, CD25 expression, and IL-2 receptor signaling. Biochem Biophys Res Commun 407:801–806CrossRefGoogle Scholar
  2. 2.
    Yaffe PB, Power Coombs MR, Doucette CD, Walsh M, Hoskin DW (2015) Piperine, an alkaloid from black pepper, inhibits growth of human colon cancer cells via G1 arrest and apoptosis triggered by endoplasmic reticulum stress. Mol Carcinog 54:1070–1085CrossRefGoogle Scholar
  3. 3.
    Harrison ME, Power Coombs MR, Delaney LM, Hoskin DW (2014) Exposure of breast cancer cells to a subcytotoxic dose of apigenin causes growth inhibition, oxidative stress, and hypophosphorylation of Akt. Exp Mol Pathol 97:211–217CrossRefGoogle Scholar
  4. 4.
    Bernard M, Furlong SJ, Power Coombs MR, Hoskin DW (2015) Differential inhibition of T lymphocyte proliferation and cytokine synthesis by [6]-gingerol, [8]-gingerol, and [10]-gingerol. Phytother Res 29:1707–1713CrossRefGoogle Scholar
  5. 5.
    Fernando W, Coombs MRP, Hoskin DW, Rupasinghe HPV (2016) Docosahexaenoic acid-acylated phloridzin, a novel polyphenol fatty acid ester derivative, is cytotoxic to breast cancer cells. Carcinogenesis 37:1004–1013CrossRefGoogle Scholar
  6. 6.
    Coombs MRP, Harrison ME, Hoskin DW (2016) Apigenin inhibits the inducible expression of programmed death ligand 1 by human and mouse mammary carcinoma cells. Cancer Lett 380:424–433CrossRefGoogle Scholar
  7. 7.
    Knekt P, Järvinen R, Seppänen R, Heliövaara M, Teppo L, Pukkala E, Aromaa A (1997) Dietary flavonoids and the risk of lung cancer and other malignant neoplasms. Am J Epidemiol 146:223–230CrossRefGoogle Scholar
  8. 8.
    Hertog MG, Feskens EJ, Hollman PC, Katan MB, Kromhout D (1994) Dietary flavonoids and cancer risk in the Zutphen elderly study. Nutr Cancer 22:175–184CrossRefGoogle Scholar
  9. 9.
    Bosetti C, Spertini L, Parpinel M, Gnagnarella P, Lagiou P, Negri E, Franceschi S, Montella M, Peterson J, Dwyer J, Giacosa A, Vecchia CL (2005) Flavonoids and breast cancer risk in Italy. Cancer Epidemiol Prev Biomark 14:805–808CrossRefGoogle Scholar
  10. 10.
    Canadian Cancer Society’s Advisory Committee on Cancer Statistics (2017) Canadian Cancer Statistics 2017. Toronto, ON: Canadian Cancer SocietyGoogle Scholar
  11. 11.
    Pedro C, Mira B, Silva P, Netto E, Pocinho R, Mota A, Labareda M, Magalhães M, Esteves S, Santos F (2018) Surgery vs. primary radiotherapy in early-stage oropharyngeal cancer. Clin Transl Radiat Oncol 9:18–22CrossRefGoogle Scholar
  12. 12.
    Maughan KL, Lutterbie MA, Ham PS (2010) Treatment of breast cancer. Am Fam Physician 81:1339–1346PubMedGoogle Scholar
  13. 13.
    Yousefi H, Yuan J, Keshavarz-Fathi M, Murphy JF, Rezaei N (2017) Immunotherapy of cancers comes of age. Expert Rev Clin Immunol 13:1001–1015CrossRefGoogle Scholar
  14. 14.
    Peters S, Reck M, Smit EF, Mok T, Hellmann MD (2019) How to make the best use of immunotherapy as first-line treatment for advanced/metastatic non-small-cell lung cancer. Ann Oncol 30:884–996CrossRefGoogle Scholar
  15. 15.
    Esteva FJ, Hubbard-Lucey VM, Tang J, Pusztai L (2019) Immunotherapy and targeted therapy combinations in metastatic breast cancer. Lancet Oncol 20:e175–e186CrossRefGoogle Scholar
  16. 16.
    Donini C, D’Ambrosio L, Grignani G, Aglietta M, Sangiolo D (2018) Next generation immune-checkpoints for cancer therapy. J Thorac Dis 10:S1581–S1601CrossRefGoogle Scholar
  17. 17.
    Alsaab HO, Sau S, Alzhrani R, Tatiparti K, Bhise K, Kashaw SK, Iyer AK (2017) PD-1 and PD-L1 checkpoint signaling inhibition for cancer immunotherapy: mechanism, combinations, and clinical outcome. Front Pharmacol 8:561CrossRefGoogle Scholar
  18. 18.
    Garcia-Lora A, Martinez M, Algarra I, Gaforio JJ, Garrido F (2003) MHC class I-deficient metastatic tumor variants immunoselected by T lymphocytes originate from the coordinated downregulation of APM components. Int J Cancer 106:521–527CrossRefGoogle Scholar
  19. 19.
    Aguiar PN, De Mello RA, Hall P, Tadokoro H, de Lima Lopes G (2017) PD-L1 expression as a predictive biomarker in advanced non-small-cell lung cancer: updated survival data. Immunotherapy 9:499–506CrossRefGoogle Scholar
  20. 20.
    Yin S-Y, Yang N-S, Lin T-J (2017) Phytochemicals approach for developing cancer immunotherapeutics. Front Pharmacol 8:386CrossRefGoogle Scholar
  21. 21.
    Apert C, Romagnoli P, van Meerwijk JPM (2018) IL-2 and IL-15 dependent thymic development of Foxp3-expressing regulatory T lymphocytes. Protein Cell 9:322–332PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Department of BiologyAcadia UniversityWolfvilleCanada
  2. 2.Department of Microbiology and ImmunologyDalhousie UniversityHalifaxCanada
  3. 3.Department of PathologyDalhousie UniversityHalifaxCanada
  4. 4.Department of SurgeryDalhousie UniversityHalifaxCanada

Personalised recommendations