Immune-related strategies driving immunotherapy in breast cancer treatment: a real clinical opportunity

Abstract

Because its original use as a treatment for hematologic disease, more recently immunotherapy has emerged as a novel effective therapeutic strategy for solid malignancies, such as melanoma and prostate carcinoma. For breast carcinoma, an immunologic therapeutic approach has not been well evaluated, even though there is evidence to suggest it would be a successful novel strategy, especially taking into account the high mortality rate of the most aggressive variants of this heterogeneous disease. Here, we briefly describe the most recently awarded immune-based therapies with a consolidated or potential implication for the treatment of solid malignancies. We focus on immune checkpoints and on the clinical potential of their abrogation, with a further overview of novel vaccine-based approaches and the most relevant immunotherapeutic techniques. We aim to provide an exhaustive review of the most promising immune-therapeutic agents that may have implications for breast cancer treatment.

Keywords:

• adoptive T-cell therapy
• breast cancer
• breast cancer therapy
• breast cancer vaccine
• immune checkpoint blockade
• ipilimumab
• pidilizumab
• tremelimumab
• vaccination

Acknowledgements

Andrea Ravelli and Laura Zanotti wish to thank ARCO Onlus-Cremona-Italy and AMOS Onlus-Pavia-Italy for their support.

Financial & competing interests disclosure

The author has 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.

Key issues

• Immune-based therapies have emerged in the past decades for the treatment of solid malignancies, including melanoma and prostate carcinoma.

• Breast carcinoma (BC) is a putatively perfect candidate for immunotherapy, because its immunogenicity is supported by a large amount of literature and because no well-assessed treatments are currently available for most-aggressive variants, such as Triple-Negative BC and Inflammatory BC.

• Immune system is heavily involved in combating BC, because its original role is to eradicate early-transforming cells. The immune-evasion phenomenon, however, permits malignant cells to proliferate through the progressive development of an immunosuppressive microenvironment, where cytotoxic lymphocytes are not effective at all.

• Immune system has been observed to play a primary role also in the mechanism of action of standard chemotherapeutic agents, which previously were thought to mediate only an immunomodulatory effect. Moreover, the observation that antibody-dependent cell-mediated cytotoxicity is a main mechanism of action of trastuzumab highlights the importance of immune system in cancer.

• The recent discovery of the mechanisms at the basis of immune-escape has rendered possible the reversal of immunosuppression and to boost cytotoxic lymphocytes activity instead; immune checkpoint blockade represents a way to enhance cytotoxic cells and to limit immunosuppression at the same time, moreover with a safety already confirmed by the clinical practice of ipilimumab for melanoma treatment.

• The development of a BC vaccine is an ongoing research field which promises some kind of success. MAGE-A3, NY-ESO-1, and MUC-1 are three tumor-associated antigens specific for BC. Their evaluation as vaccines in clinical trials is systematically ongoing, as well as many methods to enhance their effectiveness.

Notes