Immunotherapies for Breast Cancer: From Checkpoint Inhibition to Emerging Cellular Therapies

TL;DR

This paper reviews immunotherapy advances in breast cancer, focusing on checkpoint inhibitors and emerging cellular therapies like CAR-T cells to improve treatment outcomes.

Contribution

The paper highlights novel cellular immunotherapy approaches and their potential to overcome current treatment limitations in breast cancer.

Findings

Checkpoint inhibitors have shown clinical benefit in triple-negative breast cancer when combined with chemotherapy.

CAR-T cells targeting specific antigens are being explored as a next frontier in breast cancer treatment.

Emerging strategies like TIL therapy and CAR-NK platforms aim to address tumor immunosuppression and antigen barriers.

Abstract

Immunotherapy has been demonstrated to be clinically beneficial in breast cancer, particularly in subsets such as triple-negative disease. These advances provide a strong rationale for the development of cellular therapies, including CAR-T cells, to overcome the limitations of current treatments and improve outcomes in difficult-to-treat tumours. However, major challenges remain, including the identification of truly tumour-specific antigens and the immunosuppressive tumour microenvironment, both of which pose significant barriers to safety and efficacy.

Breast cancer remains a leading cause of cancer-related morbidity and mortality worldwide, with therapeutic response being shaped by the unique biology of each breast cancer subtype. Immunotherapy has emerged as a transformative approach in selected disease subtypes, with the most successful results being found in relation to triple negative breast cancer (TNBC). Immune checkpoint inhibitors (ICIs) have transformed the management of many solid tumours. In breast cancer, they have demonstrated clinical benefit in TNBC when combined with chemotherapy, establishing a new standard of care in both early-stage and metastatic settings. However, the majority of breast cancers exhibit intrinsic or acquired resistance to checkpoint blockade, driven by low tumour immunogenicity and an immunosuppressive tumour microenvironment. Recent advances in cellular immunotherapy could represent the next frontier in the therapeutic landscape of breast cancer. Chimeric antigen receptor (CAR) T cell targeting antigens such as HER2, ROR1, MUC1, mesothelin, and B7-H3 are entering early-phase clinical evaluation with results eagerly awaited. Parallel approaches, including tumour-infiltrating lymphocyte (TIL) therapy, T cell receptor (TCR)-engineered T cells, and CAR-natural killer (CAR-NK) platforms, offer alternative mechanisms to overcome antigen presentation barriers and immune evasion. This review summarises current clinical evidence for immunotherapies in breast cancer, highlights emerging cellular strategies, and discusses key challenges including antigen specificity, off-tumour toxicity, and tumour microenvironment-mediated resistance. Future progress will likely depend on rational combination approaches and next-generation engineered immune cell platforms to achieve durable and personalised clinical benefit.

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