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Updated: Jun 5, 2025
Enrichment and Characterization of the Tumor Immune and Non-immune Microenvironments in Established Subcutaneous Murine Tumors
Published on: June 7, 2018
Heterogeneity of tertiary lymphoid structures predicts the response to neoadjuvant therapy and immune
Qing Wang1, Yushuai Yu1, Chenxi Wang2
1Department of Breast Surgery, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, 350014, China.
Background:
Tertiary lymphoid structures (TLSs) impact cancer outcomes, including in triple-negative breast cancer (TNBC), where their role in immune modulation during neoadjuvant therapy (NAT) is underexplored.
Methods:
This study employed single-cell RNA sequencing (scRNA-seq), multiplex immunofluorescence (mIF) staining, and radiomic techniques to evaluate TLSs and the tumour microenvironment (TME) in TNBC patient samples before and after NAT.
Results:
The presence of TLSs in TNBC was associated with B-cell maturation and T-cell activation. Compared with TLS-low TNBC, TLS-high TNBC showed significantly greater expression of immunoglobulin family genes (IGHM and IGHG1) in B cells and greater cytotoxicity of neoantigen-specific CD8 + T cells (neoTCR8). Additionally, mIF revealed notable differences between TLSs and the TME in TNBC. Although CD8 + T-cell levels do not predict the NAT response effectively, TLS maturity strongly correlated with better NAT outcomes and prognosis (P < 0.05). An imaging biomarker scoring system was also developed to predict TLS status and NAT efficacy.
Conclusion:
Our results demonstrated changes in TLSs and the TME in TNBC patients post-NAT. These findings confirm the predictive value of mature TLSs (mTLSs) and support the use of personalised immunotherapy based on post-NAT immune characteristics, thereby improving clinical outcomes.
Insights
Mature tertiary lymphoid structures (TLSs) in triple-negative breast cancer (TNBC) predict better outcomes from neoadjuvant therapy (NAT). This study highlights TLS maturity as a key factor for personalized immunotherapy in TNBC patients.
Area of Science:
- Immunology
- Oncology
- Medical Imaging
Background:
- Tertiary lymphoid structures (TLSs) influence cancer outcomes, particularly in triple-negative breast cancer (TNBC).
- The role of TLSs in immune modulation during neoadjuvant therapy (NAT) for TNBC remains underexplored.
Purpose of the Study:
- To investigate the role and predictive value of TLSs in TNBC patients undergoing NAT.
- To characterize the tumor microenvironment (TME) and TLS composition before and after NAT.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) and multiplex immunofluorescence (mIF) staining were utilized.
- Radiomic techniques were employed to assess TLSs and the TME in TNBC patient samples.
- Analysis was performed on samples obtained before and after NAT.
Main Results:
- TLSs in TNBC are associated with B-cell maturation and T-cell activation.
- TLS-high TNBC exhibited increased immunoglobulin gene expression and enhanced CD8+ T-cell cytotoxicity.
- TLS maturity, not CD8+ T-cell levels alone, significantly correlated with better NAT response and prognosis.
- A novel imaging biomarker scoring system was developed to predict TLS status and NAT efficacy.
Conclusions:
- Neoadjuvant therapy induces changes in TLSs and the TME in TNBC patients.
- Mature TLSs (mTLSs) are confirmed as predictive biomarkers for NAT outcomes.
- Findings support personalized immunotherapy strategies based on post-NAT immune profiles to improve clinical outcomes in TNBC.
