Immunotherapy for the treatment of breast cancer

ABSTRACT

Introduction: Breast cancer is the most common cancer as well as the first cause of death by cancer in women worldwide. Although routine treatment improves the outcome of early stage breast cancer patients, there is no effective therapy for the disseminated disease. Immunotherapy has emerged as a powerful therapeutic strategy for the treatment of many cancers. Although traditionally conceived as a non-immunogenic tumor, breast cancer is now considered a potential target for immunotherapy.

Areas covered: In this review, the authors discuss different immunotherapeutic strategies that are currently being tested for the treatment of breast cancer: These strategies include: (i) blockade of immunological checkpoints, (ii) antitumor vaccines, (iii) regulatory T cell blockade, (iv) adoptive T cell transfer therapy, (iv) adoptive immunotherapy with monoclonal antibodies, and (v) combination of immunotherapy with chemotherapy.

Expert opinion: A growing body of evidence indicates that immunotherapeutic strategies can benefit a larger cohort of breast cancer patients than hitherto anticipated. Since breast tumors entail multiple mechanisms to impair antitumor immunity, the immunological characterization of individual tumors and the selection of suitable combinations of chemotherapeutic and immunotherapeutic approaches are required to achieve significant clinical benefit in these patients.

KEYWORDS:

• Breast cancer
• immunotherapy
• adoptive transfer
• immunological checkpoints
• antitumor vaccines
• regulatory T cells

Article highlights

• Breast tumor parenchyma can readily be infiltrated by lymphocytes. The grade of lymphocytes infiltration varies according to breast cancer type, being triple negative tumors the most infiltrated tumors.

• Immunosuppressive mechanisms are present in breast tumors, such as immunological checkpoints, Tregs, MDSCs, TAMs, IDO.

• Breast cancer is an excellent candidate for immunotherapeutic approaches that block immunosuppressive cells and pathways.

• Since a mechanism of tumor immune escape involves the up-regulation of immunological checkpoints, the modulation of these ligand-receptor interactions has shown promising results, and can be additionally incorporated to traditional therapies.

• Antitumor vaccines are now being reconsidered as a powerful tool for the treatment of breast cancer. They provide high specificity with good toxicological profile. Their use is being encouraged in combination with additional therapies.

• Adoptive transfer involves the extraction of peripheral T lymphocytes from patients, their expansion ex vivo and the reinfusion into the patient to target tumor cells.

• Chemotherapy can render tumors more immunogenic and hence boost the efficacy of immunotherapeutic strategies.

• Further studies are needed to fully understand the impact of immunotherapy approaches on the survival of breast cancer patients.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This work was supported by the Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET) via grants PIP 114-201101-00353 to M Candolfi.; PIP 2013-0261 to A Seilicovich and a doctoral fellowship to MA Moreno Ayala., MF Gottardo., AS Asad and the Agencia Nacional de Promoción Científica y Tecnológica via grants PICT-2012-0830; PICT-2013-0310 and PICT-2015-3309 to M Candolfi; PICT 2014-0334 to A Seilicovich and a Doctoral Fellowship to C Zuccato.