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Mechanistic insight into the immunomodulatory effects of polyphenols on breast cancer: A pharmacotherapeutic perspective (Review)

  • Authors:
    • Ritu Raina
    • Lynn Clifford Dsouza
    • Aneena Mary Shajan
    • Ravinder Bhatt
    • Arif Hussain
  • View Affiliations / Copyright

    Affiliations: Manipal Institute of Health and Life Sciences, Manipal Academy of Higher Education, Dubai Campus, P.O. Box 345050, Dubai, United Arab Emirates, Prime Health Care, Dubai 7162, United Arab Emirates
    Copyright: © Raina et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].
  • Article Number: 76
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    Published online on: July 3, 2026
       https://doi.org/10.3892/wasj.2026.491
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Abstract

Breast cancer is the leading cause of mortality and suffering among the female population worldwide. The manipulation of intrinsic immune cells and adaptive immune systems that infiltrate the tumour is merely one of several novel hypotheses that have surfaced regarding the mechanisms that support the regulation of carcinogenesis processes and related inflammatory consequences. The anticancer response and cancer‑originating inflammatory activity, which reduce antitumor immunity, coexist in the tumor microenvironment in a precarious balance. The manipulation of immune cells and inflammatory processes constitute appealing therapeutic targets in breast cancer malignancy, particularly for overcoming resistance to existing cytotoxic medications and to restore the sensitivity of cancer cells to chemotherapy. The versatile effects of dietary polyphenols in anticancer approaches have been the focus of numerous studies. A critical factor in the battle against the development of breast cancer may be the reduction of chronic inflammation or its aftereffects. This may be achieved by polyphenols via the modulation of immune checkpoints and tumor‑associated macrophages, the M1/M2 polarization, the modulation of Toll‑like receptors and the upregulation of natural killer cells in regulating T‑cell mediated immunity in breast cancer cells. The present review focuses on the most recent understanding of the potential of dietary polyphenols with a special emphasis on inhibiting breast cancer growth by altering the production of pro-inflammatory mediators and modulating the tumor environment.
View Figures

Figure 1

Illustration of the different types
of immunotherapies, namely immune checkpoint inhibitors, monoclonal
antibodies, T-cell therapy, vaccines and immune system modulators.
CTLA-4, cytotoxic T-lymphocyte antigen-4; PD-L1, programmed cell
death ligand protein 1; HER2, human epidermal growth factor
receptor 2; HER2, human epidermal growth factor receptor 2; CAR-T,
chimeric antigen receptor T-cell; IFN, interferon.

Figure 2

Illustration of the immunomodulation
of breast cancer using different pathways; immunomodulatory cells
such as T-cells, MDSCs, Tregs and macrophages; modulation of immune
checkpoints, such as PD1. PD-L1 and CTLA-4; modulation of
inflammatory cytokines and interferons; modulation of innate and
adaptive immunity; and modulation of pathways. MDSCs,
myeloid-derived suppressor cells; CTLA-4, cytotoxic T-lymphocyte
antigen-4; PD-L1, programmed cell death ligand protein 1; IL,
interleukin; IFN, interferon; MCP-1, monocyte chemoattractant
protein 1; M-CSF, macrophage colony-stimulating factor; ASC,
apoptosis-associated speck-like protein containing a CARD; IFI16,
interferon-induced protein 16; TAM, tumor-associated macrophage;
MMP, matrix metalloproteinase; Foxp3, forkhead box P3; TLR,
Toll-like receptor; NK, natural killer; DNMT, DNA
methyltransferase; HRNR.

Figure 3

Classification of phytochemicals,
classification of polyphenols into flavonoids and different types
of flavonoids.

Figure 4

Illustration depicting the modulation
of immune checkpoints, such as PD-1, PD-L1 and CTL4 by polyphenols
such as genistein, caffeic acid, resveratrol, chrysin, etc. PD-1,
programmed cell death protein 1; PD-L1, programmed cell death
ligand protein 1; CTLA-4, cytotoxic T-lymphocyte antigen-4; IL,
interleukin.

Figure 5

Illustration of the modulation of
M1/M2 polarization by polyphenols in breast cancer. IFN,
interferon; MCP-1, monocyte chemoattractant protein 1; M-CSF,
macrophage colony-stimulating factor; ROS, reactive oxygen species;
IL, interleukin.

Figure 6

Illustration depicting the role of
polyphenols in the modulation of TLRs. TLR, Toll-like receptor;
LPS, lipopolysaccharide.
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Copy and paste a formatted citation
Spandidos Publications style
Raina R, Dsouza LC, Shajan AM, Bhatt R and Hussain A: Mechanistic insight into the immunomodulatory effects of polyphenols on breast cancer: A pharmacotherapeutic perspective (Review). World Acad Sci J 8: 76, 2026.
APA
Raina, R., Dsouza, L.C., Shajan, A.M., Bhatt, R., & Hussain, A. (2026). Mechanistic insight into the immunomodulatory effects of polyphenols on breast cancer: A pharmacotherapeutic perspective (Review). World Academy of Sciences Journal, 8, 76. https://doi.org/10.3892/wasj.2026.491
MLA
Raina, R., Dsouza, L. C., Shajan, A. M., Bhatt, R., Hussain, A."Mechanistic insight into the immunomodulatory effects of polyphenols on breast cancer: A pharmacotherapeutic perspective (Review)". World Academy of Sciences Journal 8.5 (2026): 76.
Chicago
Raina, R., Dsouza, L. C., Shajan, A. M., Bhatt, R., Hussain, A."Mechanistic insight into the immunomodulatory effects of polyphenols on breast cancer: A pharmacotherapeutic perspective (Review)". World Academy of Sciences Journal 8, no. 5 (2026): 76. https://doi.org/10.3892/wasj.2026.491
Copy and paste a formatted citation
x
Spandidos Publications style
Raina R, Dsouza LC, Shajan AM, Bhatt R and Hussain A: Mechanistic insight into the immunomodulatory effects of polyphenols on breast cancer: A pharmacotherapeutic perspective (Review). World Acad Sci J 8: 76, 2026.
APA
Raina, R., Dsouza, L.C., Shajan, A.M., Bhatt, R., & Hussain, A. (2026). Mechanistic insight into the immunomodulatory effects of polyphenols on breast cancer: A pharmacotherapeutic perspective (Review). World Academy of Sciences Journal, 8, 76. https://doi.org/10.3892/wasj.2026.491
MLA
Raina, R., Dsouza, L. C., Shajan, A. M., Bhatt, R., Hussain, A."Mechanistic insight into the immunomodulatory effects of polyphenols on breast cancer: A pharmacotherapeutic perspective (Review)". World Academy of Sciences Journal 8.5 (2026): 76.
Chicago
Raina, R., Dsouza, L. C., Shajan, A. M., Bhatt, R., Hussain, A."Mechanistic insight into the immunomodulatory effects of polyphenols on breast cancer: A pharmacotherapeutic perspective (Review)". World Academy of Sciences Journal 8, no. 5 (2026): 76. https://doi.org/10.3892/wasj.2026.491
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