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Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Molecular and Clinical Characterization of LAG3 in Breast Cancer Through 2994 Samples
Qiang Liu1, Yihang Qi1, Jie Zhai1
1Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Abstract:
Despite the promising impact of cancer immunotherapy targeting CTLA4 and PD1/PDL1, numerous cancer patients fail to respond. LAG3 (Lymphocyte Activating 3), also named CD233, serves as an alternative inhibitory receptor to be targeted in the clinic. The impacts of LAG3 on immune cell populations and coregulation of immune responses in breast cancer remain largely unknown. To characterize the role of LAG3 in breast cancer, we investigated transcriptome data and associated clinical information derived from 2,994 breast cancer patients. We estimated the landscape of the relationship between LAG3 and 10 types of cell populations of breast cancer. We investigated the correlation pattern between LAG3 and immune modulators in pancancer, particularly the synergistic role of LAG3 with other immune checkpoint members in breast cancer. LAG3 expression was closely related to the malignancy of breast cancer and may serve as a potential biomarker. LAG3 may play an important role in regulating the tumor immune microenvironment of T cells and other immune cells. More important, LAG3 may synergize with CTLA4, PD1/PDL1, and other immune checkpoints, thereby contributing more evidence to improve combination cancer immunotherapy by simultaneously targeting LAG3, PD1/PDL1, and CTLA4.
Insights
Lymphocyte Activating 3 (LAG3) is a novel target for cancer immunotherapy. This study reveals LAG3
Area of Science:
- Immunology
- Oncology
- Genomics
Background:
- Cancer immunotherapy targeting CTLA4 and PD1/PDL1 shows promise but faces response limitations.
- Lymphocyte Activating 3 (LAG3), also known as CD233, presents an alternative target for immune checkpoint inhibition.
- The specific role of LAG3 in breast cancer's immune microenvironment is not well understood.
Purpose of the Study:
- To investigate the role and significance of LAG3 in breast cancer.
- To analyze the relationship between LAG3 expression and immune cell populations within breast tumors.
- To explore the potential synergistic effects of LAG3 with other immune checkpoints in breast cancer.
Main Methods:
- Analysis of transcriptome data and clinical information from 2,994 breast cancer patients.
- Estimation of LAG3's relationship with 10 distinct immune cell populations in breast cancer.
- Investigation of LAG3 correlations with immune modulators across various cancers, focusing on synergistic roles in breast cancer.
Main Results:
- LAG3 expression correlates with breast cancer malignancy and may function as a biomarker.
- LAG3 significantly influences the tumor immune microenvironment, particularly T cell populations.
- LAG3 demonstrates synergistic potential with CTLA4, PD1/PDL1, and other immune checkpoints.
Conclusions:
- LAG3 plays a crucial role in regulating the breast tumor immune microenvironment.
- Targeting LAG3, alongside CTLA4 and PD1/PDL1, could enhance combination cancer immunotherapy efficacy.
- LAG3 represents a promising therapeutic target for improving treatment outcomes in breast cancer patients.

