Mechanisms of immune evasion in breast cancer

Joshua P Bates, Roshanak Derakhshandeh, Laundette Jones, Tonya J Webb, Joshua P Bates, Roshanak Derakhshandeh, Laundette Jones, Tonya J Webb

Abstract

Tumors develop multiple mechanisms of immune evasion as they progress, with some cancer types being inherently better at 'hiding' than others. With an increased understanding of tumor immune surveillance, immunotherapy has emerged as a promising treatment strategy for breast cancer, despite historically being thought of as an immunologically silent neoplasm. Some types of cancer, such as melanoma, bladder, and renal cell carcinoma, have demonstrated a durable response to immunotherapeutic intervention, however, breast neoplasms have not shown the same efficacy. The causes of breast cancer's immune silence derive from mechanisms that diminish immune recognition and others that promote strong immunosuppression. It is the mechanisms of immune evasion in breast cancers that are poorly defined. Thus, further characterization is critical for the development of better therapies. This brief review will seek to provide insight into the possible causes of weak immunogenicity and immune suppression mediated by breast cancers and highlight current immunotherapies being used to restore immune responses to breast cancer.

Keywords: Cytokines; Dendritic cells; Immunity; Immunotherapy; Lymphocytes; Myeloid derived suppressor cells; PD-1; Regulatory T cells.

Conflict of interest statement

Competing interests

TJW is the CEO of WebbCures, LLC. The other authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Restoring T-cell activation through the use of checkpoint inhibitors. a Naïve T cells become activated following their recognition of peptides presented in the context of MHC molecules expressed on the surface of antigen presenting cells, such as dendritic cells, along with engagement of costimulatory molecules (B7) with CD28 and this activation results in upregulation of cytotoxic T-lymphocyte antigen 4 (CTLA-4). The CTLA-4 receptor on T lymphocytes is a negative regulator of T cell activation that outcompetes CD28 for binding to B7 on antigen presenting cells in order to block T cell responses. Another inhibitory pathway uses the programmed cell death 1 (PD-1) receptor. CTLA-4 and PD-1 modulate different aspects of the T cell response. CTLA-4 is rapidly induced in T cells, following activation via MHC/TCR and B7/CD28 mediated signaling. In contrast, the major role of the PD1 pathway is to regulate inflammatory responses in tissues by effector T cells recognizing antigen in peripheral tissues. b Cancers can express the ligands for these checkpoint molecules, thus blocking T cell responses. Thus, the use of checkpoint inhibitors allow T cells to maintain their effector functions via the secretion of cytokines that recruit other immune cells to participate in the antitumor response and through their cytolytic capabilities. Numerous checkpoint inhibitors are currently being used in the clinic. CTLA-4, cytotoxic T-lymphocyte antigen; PD-1, programmed death 1; PD-L1, programmed death ligand 1; APC, antigen presenting cell; MHC, major histocompatibility complex; TCR, T cell receptor
Fig. 2
Fig. 2
Adoptive T cell immunotherapy. Tumor mass can be surgically excised, fragmented, and placed in a flask, which contains T cell growth factors, such as interleukin-2 (IL-2). This will induce the proliferation of tumor-infiltrating lymphocytes, in order to expand tumor-specific T cells. Expanded tumor specific T cells will be reinfused into cancer patients in order to induce potent anti-tumor immune responses

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Source: PubMed

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