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<p>Hormone receptor-positive (HR + )/HER2-negative (HER2 − ) early breast cancers (BCs) are typically considered immunologically cold. However, combining immune checkpoint inhibitors (ICIs) with chemotherapy has shown to improve pathological complete response (pCR) in high-risk patients. Understanding the relationship between immune activation and tumor biology may help identify HR + /HER2 − BC patients most likely to benefit from such combinations. Baseline gene expression data from two neoadjuvant trials (GIADA and LETLOB) including HR + /HER2 − BC patients were analyzed. PAM50 intrinsic subtyping and relevant immune-related gene signatures were calculated. Tumor-infiltrating lymphocytes (TILs) were assessed on baseline samples. Among 109 tumors, PAM50 classified 44% as Luminal-B (LumB), 33% Luminal-A (LumA), 18% Basal-like, and 5% HER2-enriched. TIL levels (available for <i>N</i> = 101) were generally low (median 2; range 0–100), with higher levels in Basal-like BCs (<i>p</i> = 0.008). Basal-like BCs exhibited significantly higher levels of immune-related signatures (CD8 T-cells, Cytotoxic cells, IFN-γ, response to ICI + CT in GeparNuevo) and of PD-1, PD-L1, and PD-L2 genes. No differences were found between LumA and LumB subtypes. TILs and immune signatures showed a significant weak-to-moderate positive correlation with the basal-like signature. HR + /HER2- BCs that display both features of biological aggressiveness and enhanced immunogenicity may represent ideal candidates for the combination of ICI and chemotherapy.</p>

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Basal-like HR + /HER2- breast cancers show higher tumor-infiltrating lymphocytes and immune signatures with potential therapeutic implications

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月24日

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  • Gaia Griguolo,
  • Michele Bottosso,
  • Laia Paré,
  • Federica Miglietta,
  • Daniele Giulio Generali,
  • Antonino Musolino,
  • Simon Spazzapan,
  • Grazia Maria Vernaci,
  • Tommaso Giarratano,
  • Rocco Cappellesso,
  • Silvio Bicciato,
  • Federico Piacentini,
  • Enrico Tagliafico,
  • Katia Cagossi,
  • Anna Tosi,
  • Francesca Schiavi,
  • Aleix Prat,
  • Maria Vittoria Dieci,
  • Valentina Guarneri

摘要

Hormone receptor-positive (HR + )/HER2-negative (HER2 − ) early breast cancers (BCs) are typically considered immunologically cold. However, combining immune checkpoint inhibitors (ICIs) with chemotherapy has shown to improve pathological complete response (pCR) in high-risk patients. Understanding the relationship between immune activation and tumor biology may help identify HR + /HER2 − BC patients most likely to benefit from such combinations. Baseline gene expression data from two neoadjuvant trials (GIADA and LETLOB) including HR + /HER2 − BC patients were analyzed. PAM50 intrinsic subtyping and relevant immune-related gene signatures were calculated. Tumor-infiltrating lymphocytes (TILs) were assessed on baseline samples. Among 109 tumors, PAM50 classified 44% as Luminal-B (LumB), 33% Luminal-A (LumA), 18% Basal-like, and 5% HER2-enriched. TIL levels (available for N = 101) were generally low (median 2; range 0–100), with higher levels in Basal-like BCs (p = 0.008). Basal-like BCs exhibited significantly higher levels of immune-related signatures (CD8 T-cells, Cytotoxic cells, IFN-γ, response to ICI + CT in GeparNuevo) and of PD-1, PD-L1, and PD-L2 genes. No differences were found between LumA and LumB subtypes. TILs and immune signatures showed a significant weak-to-moderate positive correlation with the basal-like signature. HR + /HER2- BCs that display both features of biological aggressiveness and enhanced immunogenicity may represent ideal candidates for the combination of ICI and chemotherapy.