Immunotherapy for Breast Cancer: What Are We Missing?

Area of Science:

• Immunology
• Oncology
• Cancer Research

Background:

• Programmed death-ligand 1 (PD-L1) and programmed death receptor-1 (PD-1) antibodies demonstrate modest single-agent activity in breast cancer.
• Tumor-infiltrating T cells are prognostic for survival and predictive of response to standard therapies in breast cancer subtypes.

Discussion:

• Breast cancer exhibits lower immune cytolytic activity, tumor mutation burden, and neoepitope load compared to melanoma or lung cancer.
• Immune suppression in the tumor microenvironment and suboptimal T-cell priming are significant hurdles for breast cancer immunotherapy.
• Combinations of immunotherapeutic agents with nonredundant mechanisms are crucial for improving treatment efficacy.

Key Insights:

• Breast cancer immunotherapy requires strategies beyond targeting nonsynonymous mutations for T-cell epitopes.
• Identifying and targeting unmutated breast cancer-associated antigens is a potential avenue for enhancing immunotherapy.
• Understanding breast cancer immunobiology is critical for broadening the relevance of immunotherapy in this disease.

Outlook:

• Future breast cancer immunotherapy may involve agents that induce de novo T-cell responses.
• Combination therapies are essential for overcoming immune suppression and enhancing T-cell activity.
• Exploring novel T-cell targets, including those from unmutated antigens, will be key for advancing breast cancer immunotherapy.