# Immune-Checkpoint Expression in Breast Cancer Patients: Clinicopathological Implications: A Retrospective Case Series Study

**Authors:** Angel Quiroz-Bolaños, Antonio Quintero-Ramos, Juliana Marisol Godínez-Rubí, Ramon Franco-Topete, Porfirio Gutiérrez González, Bricia M. Gutiérrez-Zepeda, Denisse S. Becerra-Loaiza, Antonio Topete, Cesar de Loera-Rodriguez, Alicia Del Toro-Arreola, Adrián Daneri-Navarro

PMC · DOI: 10.3390/ijms26125851 · International Journal of Molecular Sciences · 2025-06-18

## TL;DR

This study examines immune-checkpoint expression in breast cancer patients and finds differences in expression patterns across tumor subtypes and grades.

## Contribution

The study identifies distinct immune-checkpoint expression profiles in different breast cancer subtypes and tumor grades, offering insights for immunotherapy strategies.

## Key findings

- Triple-negative and Her-2 tumors show higher PD-1, PD-L1, CTLA-4, and TIGIT expression compared to Luminal A and B tumors.
- High-grade tumors exhibit increased PD-1, PD-L1, LAG-3, and VISTA expression compared to lower-grade tumors.
- PD-L1/TIGIT co-expression in tumor-infiltrating cells is significantly different in triple-negative tumors compared to other subtypes.

## Abstract

Immunotherapy with antibodies targeting immune checkpoints, in combination with standard therapies, is one of the areas with the most significant clinical research, particularly in aggressive tumors such as triple-negative breast cancer, where there have been relevant advances with antibodies against PD-1/PD-L1. However, it is essential to define the biological and molecular factors that influence survival and response to immunotherapy, as other immune control points, such as CTLA-4, TIM-3, LAG-3, TIGIT, and VISTA, also play a role. The immune checkpoints were studied by microarrays and immunohistochemistry in 243 samples from patients with breast cancer, according to the molecular subtype. Significant differences in PD-1, PL-1, CTLA-4, and TIGIT expression were observed between triple-negative and Her-2 tumors compared to Luminal A and Luminal B tumors. No differences in VISTA expression were observed between the different molecular subtypes. Patients with high-grade tumors showed higher PD-1, PD-L1, LAG-3, and VISTA expression than low and intermediate-grade tumors. We observed a significant difference in PD-L1/TIGIT co-expression in tumor-infiltrating cells from patients with triple-negative tumors compared to patients with Luminal A, Luminal B, and Her2+ tumors. These results are relevant in the context of clinical application.

## Linked entities

- **Proteins:** PDCD1 (programmed cell death 1), CD274 (CD274 molecule), CTLA4 (cytotoxic T-lymphocyte associated protein 4), HAVCR2 (hepatitis A virus cellular receptor 2), LAG3 (lymphocyte activating 3), TIGIT (T cell immunoreceptor with Ig and ITIM domains), VSIR (V-set immunoregulatory receptor)
- **Diseases:** breast cancer (MONDO:0004989), triple-negative breast cancer (MONDO:0005494)

## Full-text entities

- **Genes:** VSIR (V-set immunoregulatory receptor) [NCBI Gene 64115] {aka B7-H5, B7H5, C10orf54, DD1alpha, Dies1, GI24}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, LAG3 (lymphocyte activating 3) [NCBI Gene 3902] {aka CD223}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493] {aka ALPS5, CD, CD152, CELIAC3, CTLA-4, GRD4}, HAVCR2 (hepatitis A virus cellular receptor 2) [NCBI Gene 84868] {aka CD366, HAVcr-2, KIM-3, SPTCL, TIM3, TIMD-3}, TIGIT (T cell immunoreceptor with Ig and ITIM domains) [NCBI Gene 201633] {aka VSIG9, VSTM3, WUCAM}
- **Diseases:** triple-negative breast cancer (MESH:D064726), tumor (MESH:D009369), Breast Cancer (MESH:D001943)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12193408/full.md

## References

15 references — full list in the complete paper: https://tomesphere.com/paper/PMC12193408/full.md

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Source: https://tomesphere.com/paper/PMC12193408