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Heterogeneity of tertiary lymphoid structures predicts the response to neoadjuvant therapy and immune microenvironment characteristics in triple-negative breast cancer. | LitMetric
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.
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