Related Experiment Video
Updated: Dec 17, 2025
Predictive Immune Modeling of Solid Tumors
Published on: February 25, 2020
Prognostic value of immune checkpoint molecules in breast cancer
Jun Fang1,2,3, Feng Chen1,4, Dong Liu1,2,3
1Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Zhejiang, Hangzhou 310022, People's Republic of China.
Abstract:
Immune checkpoint blockade treatments bring remarkable clinical benefits to fighting several solid malignancies. However, the efficacy of immune checkpoint blockade in breast cancer remains controversial. Several clinical trials of immune checkpoint blockades focused on the effect of CTLA4 and PD1/PDL1 checkpoint inhibitors on breast cancer. Only a small portion of patients benefited from these therapies. Here we systematically investigated the expression of 50 immune checkpoint genes, including ADORA2A, LAG-3, TIM-3, PD1, PDL1, PDL2, CTLA-4, IDO1, B7-H3, B7-H4, CD244, BTLA, TIGIT, CD80, CD86, VISTA, CD28, ICOS, ICOSLG, HVEM, CD160, LIGHT, CD137, CD137L, OX40, CD70, CD27, CD40, CD40LG, LGALS9, GITRL, CEACAM1, CD47, SIRPA, DNAM1, CD155, 2B4, CD48, TMIGD2, HHLA2, BTN2A1, DC-SIGN, BTN2A2, BTN3A1, BTNL3, BTNL9, CD96, TDO, CD200 and CD200R, in different subtypes of breast cancer and assessed their prognostic value. The results showed that the expression patterns of these 50 immune checkpoint genes were distinct in breast cancer. High expression of B7-H3 mRNA was significantly associated with worse overall survival (OS), especially in patients with luminal A and luminal B breast cancer. The mRNA expression levels of TIM-3, ADORA2A, LAG3, CD86, CD80, PD1 and IDO1 had no relationship with OS in breast cancer. High expression levels of CTLA-4 and TIGIT were correlated with favorable prognosis in breast cancer. Interestingly, we observed that B7-H3 expression was negatively correlated with the efficacy of cyclophosphamide (CTX). In summary, our study suggested that B7-H3 has potential prognostic value in breast cancer and is a promising target for immune therapy.
Insights
Immune checkpoint blockade efficacy in breast cancer is debated. This study found B7-H3 expression indicates poor prognosis and may predict response to chemotherapy, suggesting it as a potential therapeutic target.
Area of Science:
- Immunology
- Oncology
- Genetics
Background:
- Immune checkpoint blockade (ICB) offers benefits in solid tumors, but its efficacy in breast cancer is inconsistent.
- Clinical trials targeting CTLA4 and PD1/PDL1 have shown limited success in breast cancer patients.
- Understanding the role of various immune checkpoints is crucial for improving breast cancer treatment.
Purpose of the Study:
- To systematically investigate the expression of 50 immune checkpoint genes in different breast cancer subtypes.
- To assess the prognostic value of these immune checkpoint genes in breast cancer.
- To explore the potential of immune checkpoints as therapeutic targets in breast cancer.
Main Methods:
- Comprehensive analysis of mRNA expression levels for 50 immune checkpoint genes across breast cancer subtypes.
- Statistical evaluation of the correlation between gene expression and overall survival (OS).
- Investigation of the relationship between B7-H3 expression and cyclophosphamide (CTX) efficacy.
Main Results:
- Distinct expression patterns of 50 immune checkpoint genes were observed in breast cancer.
- High B7-H3 mRNA expression was significantly associated with worse OS, particularly in luminal A and B subtypes.
- High CTLA-4 and TIGIT expression correlated with favorable prognosis, while TIM-3, ADORA2A, LAG3, CD86, CD80, PD1, and IDO1 showed no OS association.
- B7-H3 expression was negatively correlated with cyclophosphamide efficacy.
Conclusions:
- B7-H3 exhibits potential as a prognostic biomarker in breast cancer.
- B7-H3 represents a promising target for novel immune therapies in breast cancer.
- Understanding immune checkpoint expression profiles can guide personalized treatment strategies.
