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<p>Despite recent therapeutic advances, triple-negative breast cancer (TNBC) remains therapeutically challenging. To better define the biological basis of clinically relevant therapeutic targets, we investigated the immune landscape of PD-L1, PD1, and TROP2 in TNBC. Transcriptome and clinical data from 1,500 primary TNBC patients were analyzed to compare immune-related gene expression patterns between high and low expression of <i>CD274</i> (PD-L1), <i>TACSTD2</i> (TROP2), and <i>PDCD1</i> (PD1). Pathway enrichment analyses were complemented by immunohistochemical validation in an independent breast cancer (BC) cohort (<i>n</i> = 271), and associations with patient survival were evaluated. PD-L1–high TNBCs exhibited a strongly immune-inflamed but immunoregulatory phenotype with enrichment of interferon-related and chemokine-driven pathways. In contrast, TROP2-positive tumors showed a distinct epithelial differentiation program consistent with immune exclusion, rather than classical immune activation. Protein-level validation confirmed increased CXCL13 and CD79a expression and higher immune infiltration in PD-L1–high tumors. Survival analyses demonstrated improved RFS in patients with low PD-L1 expression and improved OS in patients with low PD-L1 and low PD1 expression, whereas elevated TROP2 protein levels correlated with prolonged OS in TNBC patients. Together, these findings demonstrate that PD-L1– and TROP2-defined subgroups represent distinct immune-inflamed and epithelial-driven immune-excluded phenotypes, providing a rationale for biomarker-guided therapeutic strategies in TNBC.</p>

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Immune landscape in PD-L1- and TROP2-positive triple-negative breast cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月4日

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  • Gyongyi Munkacsy,
  • Gabor Lotz,
  • Anna Maria Tokes,
  • Libero Santarpia,
  • Balazs Gyorffy

摘要

Despite recent therapeutic advances, triple-negative breast cancer (TNBC) remains therapeutically challenging. To better define the biological basis of clinically relevant therapeutic targets, we investigated the immune landscape of PD-L1, PD1, and TROP2 in TNBC. Transcriptome and clinical data from 1,500 primary TNBC patients were analyzed to compare immune-related gene expression patterns between high and low expression of CD274 (PD-L1), TACSTD2 (TROP2), and PDCD1 (PD1). Pathway enrichment analyses were complemented by immunohistochemical validation in an independent breast cancer (BC) cohort (n = 271), and associations with patient survival were evaluated. PD-L1–high TNBCs exhibited a strongly immune-inflamed but immunoregulatory phenotype with enrichment of interferon-related and chemokine-driven pathways. In contrast, TROP2-positive tumors showed a distinct epithelial differentiation program consistent with immune exclusion, rather than classical immune activation. Protein-level validation confirmed increased CXCL13 and CD79a expression and higher immune infiltration in PD-L1–high tumors. Survival analyses demonstrated improved RFS in patients with low PD-L1 expression and improved OS in patients with low PD-L1 and low PD1 expression, whereas elevated TROP2 protein levels correlated with prolonged OS in TNBC patients. Together, these findings demonstrate that PD-L1– and TROP2-defined subgroups represent distinct immune-inflamed and epithelial-driven immune-excluded phenotypes, providing a rationale for biomarker-guided therapeutic strategies in TNBC.