# JAK/STAT-mediated regulation of PD-L1 expression in breast cancer: Molecular mechanisms and implications for immunotherapy

## TL;DR

This paper explores how JAK/STAT signaling controls PD-L1 in breast cancer, offering insights into immune evasion and better immunotherapy strategies.

## Contribution

The paper provides a comprehensive review of JAK/STAT's role in PD-L1 regulation, linking inflammation, tumor stress, and immune evasion in breast cancer.

## Key findings

- JAK/STAT signaling, especially STAT1 and STAT3, regulates PD-L1 expression in breast cancer cells and immune cells.
- Cytokines, hypoxia, and extracellular vesicles sustain STAT-dependent PD-L1 programs that hinder immune responses.
- Combination therapies targeting JAK/STAT and immune checkpoints may improve treatment outcomes in breast cancer.

## Abstract

Immune checkpoint blockade targeting the PD-1/PD-L1 axis has expanded treatment options for breast cancer, particularly triple-negative disease, yet therapeutic responses are limited by immune escape mechanisms. This review synthesizes mechanistic evidence showing how JAK/STAT signaling, predominantly through STAT1 and STAT3, integrates inflammatory cues, oncogenic stress, and microenvironmental signals to regulate PD-L1 expression across tumor cells and immune compartments. Experimental studies using cell lines, patient specimens, and in vivo models reveal that cytokines, hypoxia, metabolic remodeling, and extracellular vesicles sustain STAT-dependent PD-L1 programs that dampen cytotoxic immunity and promote resistance to therapy. The review further examines pharmacologic, genetic, and nanotechnology-based strategies that disrupt this signaling axis and enhance immune checkpoint efficacy, including combination regimens with chemotherapy, targeted therapy, and photodynamic approaches. Collectively, these findings position JAK/STAT-driven PD-L1 regulation as a unifying framework for understanding immune evasion and optimizing immunotherapy in breast cancer.

Biological sciences