Classes of therapeutics to amplify the immune response

Abstract

Purpose: Conventional chemotherapies are a mainstay for metastatic breast cancers, though durable response is rare. Immunotherapies promise long-term responses thorough immune activation but have been underwhelming in breast cancer relative to other cancer types. Here, we review the mechanisms of existing strategies including chemotherapies and how they may cause breast cancers to become immunogenic to identify potential biomarkers for combinations of conventional and immunotherapies.

Conclusion: Mechanistic considerations should inform biomarker development and patient selection for therapeutic combinations of drugs to combine with immune-checkpoint inhibitors.

Keywords: Immunogenic cell death; T-cell activation; Targeted therapies; Taxane; cGAS-STING.

Figure 1.. Mechanisms of immune activation by breast cancer therapies

General schema of immune activation mechanisms. The outer ring (blue) represents potential biomarkers and types of therapies that can result in six immune-activating effects shown in the middle ring (purple), which are the increase of surface immune markers, induction of immunogenic cell death, activation of cGAS-STING, promotion of immune cytotoxicity, modulation of innate immune cells, and recruitment of T-cells. Furthermore, these immune-activating effects in the middle ring (purple) can result in downstream activation of other immune processes shown in the inner ring (pink). Ultimately, these downstream effects can feedback into the other immune-activating processes shown in the middle (purple) and outer (blue) rings, resulting in multiple immune-activating effects from one type of therapy or mechanism.