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Review
. 2014 Jan;15(1):1-15.
doi: 10.1631/jzus.B1300264.

Harnessing the immune system for the treatment of breast cancer

Affiliations
Review

Harnessing the immune system for the treatment of breast cancer

Xinguo Jiang. J Zhejiang Univ Sci B. 2014 Jan.

Abstract

Standard treatment options for breast cancer include surgery, chemotherapy, radiation, and targeted therapies, such as adjuvant hormonal therapy and monoclonal antibodies. Recently, the recognition that chronic inflammation in the tumor microenvironment promotes tumor growth and survival during different stages of breast cancer development has led to the development of novel immunotherapies. Several immunotherapeutic strategies have been studied both preclinically and clinically and already have been shown to enhance the efficacy of conventional treatment modalities. Therefore, therapies targeting the immune system may represent a promising next-generation approach for the treatment of breast cancers. This review will discuss recent findings that elucidate the roles of suppressive immune cells and proinflammatory cytokines and chemokines in the tumor-promoting microenvironment, and the most current immunotherapeutic strategies in breast cancer.

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Conflict of interest statement

Compliance with ethics guidelines: Xinguo JIANG declares that he has no conflict of interest.

This article does not contain any studies with human or animal subjects performed by the author.

Figures

Fig. 1
Fig. 1
M2-polarized TAM promotes breast cancer progression, metastasis, treatment resistance and recurrence COX-2 or STAT3 activation polarizes TAM to the M2 phenotype. Expression of microRNA miR-19a-3p in TAM or low dose anti-VEGFR2 treatment polarizes TAM to the M1 phenotype. TAM promotes angiogenesis by producing VEGF, FGF-2, IL-1, and IL-8. TAM also promotes breast cancer cell proliferation by producing EGF, FGF-2, IL-6, TGF-β, and PDGF. In addition, TAM promotes the breast cancer stem cell phenotype by producing EGF, IL-6, and IL-8 or by fusing with breast cancer cells. Lastly, TAM promotes breast cancer cell invasiveness by producing MMPs and EGF. Abbreviations: TAM, tumor-associated macrophage; COX-2, cyclooxygenase 2; STAT3, signal transducer and activator of transcription 3; VEGF, vascular endothelial growth factor; VEGFR, VEGF receptor; FGF, fibroblast growth factor; IL, interleukin; TGF, transforming growth factor; PDGF, platelet-derived growth factor; EGF, epidermal growth factor; MMP, matrix metalloproteinase; BCC, breast cancer cell; BCSC, breast cancer stem cell
Fig. 2
Fig. 2
Scheme of immunotherapeutic strategies Antitumor immunity can be boosted by antagonizing suppressive factors, such as TGF-β, IL-10, IDO, and PGE2, inhibition of immune checkpoints, and therapeutic vaccines. Proinflammatory mediators, such as IL-6, IL-8, IL-1, TNF-α, CCL5, CCL2, CXCL10 and CXCL12, can also be targeted. Moreover, depleting or reprogramming suppressive immune cells, such as Treg cells, TAM, or B cells, can also indirectly boost antitumor immunity. Immunotherapy combined with conventional therapies will likely improve the overall therapeutic efficacy. Abbreviations: TGF, transforming growth factor; IL, interleukin; PG, prostaglandin; IDO, indoleamine-pyrrole 2,3-dioxygenase; TNF, tumor necrosis factor; CXCL, chemokine (C-X-C motif) ligand; CCL, CC chemokine ligand; CSF, colony stimulating factor; COX-2, cyclooxygenase-2; STAT3, signal transducer and activator of transcription 3
Fig. 3
Fig. 3
Dr. Xinguo JIANG

References

    1. Aceto N, Duss S, Macdonald G, et al. Co-expression of HER2 and HER3 receptor tyrosine kinases enhances invasion of breast cells via stimulation of interleukin-8 autocrine secretion. Breast Cancer Res. 2012;14(5):R131. doi: 10.1186/bcr3329. - DOI - PMC - PubMed
    1. Acharyya S, Oskarsson T, Vanharanta S, et al. A CXCL1 paracrine network links cancer chemoresistance and metastasis. Cell. 2012;150(1):165–178. doi: 10.1016/j.cell.2012.04.042. - DOI - PMC - PubMed
    1. Basu S, Nachat-Kappes R, Caldefie-Chezet F, et al. Eicosanoids and adipokines in breast cancer: from molecular mechanisms to clinical considerations. Antioxid Redox Signal. 2013;18(3):323–360. doi: 10.1089/ars.2011.4408. - DOI - PubMed
    1. Bates GJ, Fox SB, Han C, et al. Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. J Clin Oncol. 2006;24(34):5373–5380. doi: 10.1200/JCO.2006.05.9584. - DOI - PubMed
    1. Baumgarten SC, Frasor J. Minireview: Inflammation: an instigator of more aggressive estrogen receptor (ER) positive breast cancers. Mol Endocrinol. 2012;26(3):360–371. doi: 10.1210/me.2011-1302. - DOI - PMC - PubMed

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