# Immunotherapy Approaches for the Treatment of Triple-Negative Breast Cancer

## TL;DR

This review discusses current and emerging immunotherapy strategies for triple-negative breast cancer, focusing on improving treatment outcomes through immune checkpoint inhibition, cell therapies, and combination approaches.

## Contribution

The paper provides a comprehensive overview of immunotherapeutic approaches and resistance mechanisms in triple-negative breast cancer.

## Key findings

- Immunotherapy responses in TNBC are limited due to immune escape mechanisms like DNA damage response alterations and immunosuppressive tumor microenvironments.
- Combination strategies involving immunotherapy with chemotherapy or targeted therapy show potential to enhance antitumor immune responses.
- Emerging approaches such as adoptive cell therapy and oncolytic virotherapy are being explored to improve treatment outcomes in TNBC.

## Abstract

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with limited treatment options and poor clinical outcomes. Despite its relatively high immunogenicity, responses to immunotherapy remain restricted to a subset of patients. This narrative review provides a comprehensive overview of current and emerging immunotherapeutic approaches for TNBC including immune checkpoint inhibition, adoptive cell therapies, oncolytic viruses, and antibody-based strategies. We also summarize key molecular and cellular mechanisms that limit therapeutic efficacy such as alterations in DNA damage response pathways, activation of anti-apoptotic signaling and immunosuppressive features of the tumor microenvironment. Finally, we discuss rational combination strategies designed to enhance antitumor immune responses. Ongoing advances in immunotherapy hold significant potential to improve outcomes for patients with TNBC.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by high immunogenicity and specific immune signatures. Although these molecular features including elevated tumor-infiltrating lymphocytes (TILs) and programmed death-ligand 1 (PD-L1) expression provide a strong rationale for immunotherapy, clinical response remains limited due to multiple mechanisms of immune escape. This review summarizes current and emerging immunotherapeutic strategies in TNBC, including immune checkpoint inhibitors (PDL-1 and cytotoxic T-lymphocyte-associated protein 4 (CTL-4) blockade), adoptive cell therapy (ACT) (chimeric antigen receptor T-cell therapy (CAR-T) and TIL therapy), oncolytic virotherapy, and antibody-based approaches. We also discuss the mechanisms of resistance including DNA damage response alterations, anti-apoptotic signaling, and tumor microenvironment-mediated resistance. Finally, we highlight rational combination strategies, immunotherapy with chemotherapy, targeted therapy, or additional immunotherapies that aim to enhance response to immunotherapy. Ongoing advances in immunotherapy hold significant potential to improve outcomes for patients with TNBC.