Journal Article Ppublish
PubMed: 40744683 DOI: 10.1002/cnr2.70291
Co-Expression of MHC-II and ANXA1: Mediators of PD-1/PD-L1 Therapy Resistance in Breast Cancer.
Cancer Rep (Hoboken) 8(8):e70291
Authors: Hao Wang, Ji-Feng Sun, Chen Wang, Zhan-Sheng Jiang, Zhong-Sheng Tong
Affiliations
- Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin, China. Tianjin's Clinical Research Center for Cancer, Tianjin, China. Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, China. Key Laboratory of Cancer Prevention and Therapy, Tianjin, China. Tianjin Cancer Hospital Airport Hospital, Tianjin, China.
- Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin, China. Tianjin Cancer Hospital Airport Hospital, Tianjin, China.
- Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin, China. Tianjin's Clinical Research Center for Cancer, Tianjin, China. Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, China. Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
- Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin, China.
- Tianjin's Clinical Research Center for Cancer, Tianjin, China.
- Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, China.
- Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
Abstract
BACKGROUND
Triple-negative breast cancer (TNBC) presents significant treatment challenges and poor prognosis. While immune checkpoint blockade (ICB) therapy shows promise, patient responses vary widely, highlighting the urgent need for reliable biomarkers to predict efficacy and guide treatment decisions.
AIMS
This study aims to investigate the role of Major Histocompatibility Complex class II (MHC-II) expression in breast cancer, specifically focusing on its impact on immune evasion, tumor metastasis, and immunotherapy efficacy. The objective is to emphasize the necessity of targeted research in order to enhance therapeutic strategies for TNBC.
METHODS
We employed Limma for conducting differential expression analysis, clusterProfiler for performing GO and KEGG pathway enrichment analyses, and Mendelian randomization analyses utilizing data from the UK Biobank and GEO data sets. Single-cell sequencing data were analyzed using Scanpy and CellTypist, where UMAP, PCA, and the Leiden algorithm were applied to explore cellular heterogeneity as well as gene expression profiles.
RESULTS
We observed significant differential gene expression between MHC-II-high and MHC-II-low hematopoietic stem cells, which has an impact on immune responses and cancer pathways, particularly in TNBC. Mendelian randomization analysis identified key genes associated with breast cancer risk and PD-L1 status. Additionally, ANXA1 was significantly decreased in expression in breast cancer tissues compared to normal tissues and demonstrated increased expression in nonresponders to PD-1/PD-L1 therapies in TNBC patients, suggesting its potential involvement in immunotherapy resistance despite lacking a direct correlation with overall survival rates.
CONCLUSION
The findings of this study highlight the potential role of ANXA1 in mediating resistance to PD-1/PD-L1 therapy in breast cancer, which is associated with MHC-II expression. ANXA1 could serve as both a predictive marker for treatment resistance and a therapeutic target to enhance the efficacy of immunotherapy.
MeSH
Cells, Genes, Major Histocompatibility Complex, Breast Neoplasms, Neoplasms, Immunotherapy, Breast, Therapeutics, Tissues, Random Allocation, Gene Expression
Cited by
- Co-Expression of MHC-II and ANXA1: Mediators of PD-1/PD-L1 Therapy Resistance in Breast Cancer. Cancer Rep (Hoboken), 2025