The Trojan Horse Within: Mechanisms of Immune Evasion in Breast Cancer

TL;DR

This review explores how breast cancer cells evade the immune system and discusses strategies to overcome these evasion mechanisms for better treatment.

Contribution

The paper provides a comprehensive overview of immune evasion mechanisms in breast cancer subtypes and their clinical implications.

Findings

TNBCs expressing PD-L1 show improved responses to immune checkpoint inhibitors.

Tumor heterogeneity and cellular plasticity contribute to immune evasion in breast cancer.

Immune-suppressive cells in the tumor microenvironment help cancer cells avoid detection.

Abstract

Breast cancer (BC) is the most common type of cancer among females, and the number of deaths due to BC has increased over the past few decades. BC is primarily categorized based on the receptor status of BC cells as hormone receptor-positive (HR+), human epidermal growth factor receptor 2-positive (HER2+), and triple-negative BC (TNBC). These subtypes differ significantly in their treatment strategies, prognosis, immunogenic nature, and response to immunotherapy. TNBC is the most aggressive with a poor prognosis, but a subset of TNBCs that express programmed cell death ligand 1, have shown promising responses to immune checkpoint inhibitors. Across BC subtypes, distinct immune cell subsets remain active in the tumor immune microenvironment (TIME) that either inhibit or promote the growth of cancer. In isolation, it is challenging for cancer cells to thrive in presence of the body’s immune system, however with the aid of other cells in the TIME, they can work together to evade immune detection by suppressing antigen presentation, modulating immune recognition markers, and recruiting immune-suppressive cells. In this review, we provide an overview of the BC immune evasion mechanisms and discuss aspects of immune evasion in relation to tumor heterogeneity and cellular plasticity. We also highlight successful clinical trials targeting immune-evasion markers and discuss the challenges and potential future directions for solving these problems.

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